Theresa Beckie, PhD, of the USF College of Nursing, compared the physical and psychosocial effects of a traditional cardiac rehabilitation to a program geared specifically for women.

ORLANDO, FL. (Nov. 17, 2009) — Depressive symptoms improved among women with coronary heart disease who participated in a motivationally-enhanced cardiac rehabilitation program exclusively for women, according to research presented at the American Heart Association’s Scientific Sessions 2009.

Depression often co-occurs with heart disease and is found more often in women with heart disease than in men. Depression also interferes with adherence to lifestyle modifications and the willingness to attend rehabilitation.

“Women often don’t have the motivation to attend cardiac rehab particularly if they’re depressed,” said Theresa Beckie, Ph.D., lead investigator and author of the study and professor at the University of South Florida’s College of Nursing in Tampa, FL. “Historically women have not been socialized to exercise and their attendance in cardiac rehabilitation programs has been consistently poor over the last several decades. This poor attendance may be partly due to mismatches in stages of readiness for behavior change with the health professional approaching from an action-oriented perspective and the women merely contemplating change --- this is destined to evoke resistance.”

Cardiac rehabilitation programs tailored to the needs of women and to their current level of readiness to change may improve adherence to such programs and potentially improve outcomes for women, she said.

The primary goals of the 5-year randomized clinical trial were to compare multiple physiological and psychosocial outcomes of women who participated in a 12-week stage-of-change matched, motivationally enhanced, gender-tailored cardiac rehabilitation program exclusively for women compared to women attending a 12-week traditional cardiac rehabilitation program comprised of education and exercise. Depressive symptoms of 225 women (average age 63) who completed this trial were examined after the interventions as well as after a 6-month follow-up period.

Women with cardiac disease have unique needs and confront different challenges than men in adopting healthy behaviors as they recover, Beckie says.

Participants completed the 20-item Center for Epidemiological Studies Depression Scale prior to beginning the intervention, one week after completing the intervention, and again six months later. The questionnaire asked them about how often in the past week they felt depressed, hopeful, lonely, happy and fearful.

Depression scores for the women participating in the traditional cardiac rehab dropped from 16.5 to 14.3 in 12 weeks, while scores in the augmented group dropped from 17.3 to 11.0 – “a significant decline compared to the traditional group,” said Beckie.

After a six-month follow-up, the traditional rehab group had an average score of 15.2 and those in the women-specific program had a mean score of 13. Beckie said “we found that improvements in depressive symptoms were sustained at the 6-month follow-up in the augmented group while those in traditional cardiac rehab were essentially unchanged. This intervention also led to significantly better attendance and completion rates than those in the traditional cardiac rehabilitation program.”

The intervention was guided by the transtheoretical model of behavior change and was delivered with motivational interviewing clinical methods. The motivationally-enhanced intervention began with an assessment of their stage of motivational readiness to change regarding three behaviors: healthy eating, physical activity, and stress management. The investigators then applied appropriate stage-matched strategies to promote the uptake of health behaviors.

“The stage-matched intervention used in conjunction with motivational interviewing applied the patient-centered principles of expressing empathy, rolling with resistance to change, respecting patient autonomy and supporting self-efficacy for change” Beckie said.

“We didn’t push them if they weren’t ready to make the changes,” Beckie said. “We have found that if some patients receive long lists of behaviors they are expected to change immediately — such as quitting smoking, eating healthier, exercising regularly — they are overwhelmed. Pushing such patients who are not ready can lead them to tune out or drop out. Instead, for these women, we acknowledged their ambivalence about change and gave them strategies to move toward being ready by reinforcing their own motivations for changing. It’s unrealistic to expect all patients to change their lifestyle all at once, right now in front of you.”

The positive impact of the women-centered program remained six months after the 12-week study ended.

The woman-centered program is a more individualized approach to rehabilitation.

“You can’t treat everyone the same when it comes to changing health behaviors,” she said.

Beckie hopes these results will lead to symptoms of depression being assessed more often in women suffering from heart disease and to more motivationally augmented, women-specific rehabilitation options. The participants may not be completely representative of the national population because they all had health insurance.

Beckie’s co-author is Jason Beckstead, PhD. The National Institute of Nursing Research funded the 5-year study.

- USF Health -

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

The USF arm of the NIH trials will be performed at Genesis, Tampa General Hospial and USF clinics.

Tampa, FL (Oct. 26, 2009) -- The University of South Florida is participating in two federal studies to see whether the H1N1 vaccine can safely elicit a protective immune response in pregnant women, as well as in children and young adults, all of whom are HIV-infected.

USF will be one of 35 sites and eight sub-sites in the United States and Puerto Rico participating in the two studies, which are sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both part of the National Institutes of Health. Investigators plan to vaccinate about 130 HIV-infected women and 140 HIV-infected children and young adults around the country.

USF is participating in both studies as part of its role as a site of the International Maternal-Pediatric-Adolescent AIDS Clinical Trials Group (IMPAACT) network, a project of NIAID and NICHD that develops and implements multi-center HIV treatment and prevention research trials.

In the first study, on HIV-infected pregnant women, about 10 women are expected to be enrolled in the Tampa Bay area, said Dr. Karen L. Bruder, USF assistant professor of obstetrics and gynecology and the principal investigator for USF’s study site. Dr. Bruder also is medical director of the Genesis at HealthPark clinic of Tampa General Hospital.

The study is particularly important for this group of women because pregnant women already are at greater risk of suffering serious complications from the H1N1 virus, largely because their immune systems do not function at their normal levels. If a pregnant woman also is infected with HIV, her immune system is further compromised.

“She is already immuno-suppressed,” Dr. Bruder said.

Dr. Karen Bruder leads the USF study site testing whether the H1N1 vaccine protects HIV-infected pregnant women.

The study will look at how the vaccine affects the woman and her infant -- for instance, how many antibodies to the H1N1 influenza virus does the woman develop in response to the vaccine? Are those antibodies transferred to the fetus? After the baby is born, does it still have antibodies to the virus?

The study will also evaluate whether the vaccine affects the woman’s HIV viral load or the cells in the immune system that are often affected by HIV.

Women in the study will receive two doses of vaccine. The women’s response to the vaccine will be evaluated during pregnancy, at delivery, and at 3 and 6 months after delivery. The babies will be evaluated when they are 3 and 6 months old.

USF’s work in the study will be performed at Genesis, Tampa General and at USF clinics.
In the second study, at least four HIV-infected children or young adults will receive the H1N1 vaccine at the USF clinics, said Dr. Jorge Lujan-Zilbermann, associate professor of pediatrics and principal investigator for the USF site of the study.

This study will divide subjects into three age groups: ages 4 to 9, 10 to 17, and 18 to 24. As in the first study, the children and young adults will receive vaccine in two doses three weeks apart. Study subjects will be followed for seven months.

The study will examine how safe the vaccine is, how effectively it stimulates the immune system to make antibodies to the H1N1 influenza virus, and how long children and young adults maintain these antibodies in their blood after being vaccinated. The study will also look at other immune responses.

The vaccine all study subjects will receive contains inactivated virus, so it will not be possible for them to contract H1N1 influenza from the vaccine. Because of the increased vulnerability of HIV-infected pregnant women, children and youth, the trials will test whether doses of the licensed 2009 H1N1 influenza vaccine that are higher than doses being tested in other groups can safely elicit protective immune responses in these populations.

The IMPAACT sites participating in these studies will receive vaccine from Novartis Vaccines and Diagnostics of Cambridge, Mass, through the Office of the Assistant Secretary for Preparedness and Response for the U.S. Department of Health and Human Services.

For more information about NIH-sponsored clinical trials of H1N1 influenza vaccine in HIV-infected pregnant women, children and youth, see http://www3.niaid.nih.gov/news/newsreleases/2009/H1N1HIVTrials.htm and http://www3.niaid.nih.gov/news/QA/H1N1VacHIVChildYouthPregWomenqa.htm

- USF Health -

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.health.usf.edu

- Story by Lisa Greene, USF Health Communications
- Photos by Eric Younghans, USF Health Communications

USF is one three sites for the $1-million study, sponsored by the National Institute of Child Health and Development (NICHD) through the American Recovery and Reinvestment Act. The other two sites are the University of California at Los Angeles and the University of Miami. The USF arm of the study will receive approximately $500,000.

USF's Eric Storch, PhD, is principal investigator for the multi-site behavioral therapy trial.

Autism spectrum disorders, collectively referred to as autism, cause pervasive impairment in thinking, feeling, language and the ability to relate to others and can range from a severe from (called autistic disorder) to a much milder form known as Asperger syndrome. Anxiety disorders affect as many as 80 percent of children and adolescents with autism spectrum disorders, triggering distress and impairment over and above that caused by an autism diagnosis alone, said Eric Storch, PhD, principal investigator for the multi-site trial and associate professor of pediatrics and psychiatry at USF Health.

“As yet, there are no tried-and-true methods for treating the anxiety that often accompanies autism,” Dr. Storch said. “Cognitive behavioral therapy has worked very well for typically developing kids with anxiety. The goal of this study is to adapt this therapy for use in early adolescents with autism and co-occurring anxiety.”

Cognitive behavioral therapy (CBT) involves exposing a patient to what they fear in controlled, graduated doses in an attempt to decrease their anxiety over time and prevent a compulsive or avoidance response. It has become a gold standard treatment for youngsters with anxiety disorders who do not have complicating conditions like autism or attention deficit hyperactivity disorder.

The researchers will first adapt a CBT protocol they have developed for younger children to meet the characteristics and clinical needs of early adolescents (ages 11 to 14) with autism. They will accomplish this by treating numerous youngsters and consulting with other autism experts. Then, the team will enroll 32 adolescents with autism in a randomized trial across the sites. The participants will receive either the newly developed CBT protocol or a modified relaxation training protocol (control group). Those who receive the control treatment will receive CBT afterwards.

“Considering the rising number of young adolescents diagnosed with autism, and the lack of proven treatment options for those suffering from anxiety,” Dr. Storch said, “our work developing a treatment protocol could substantially help address the mental health needs of early adolescents with autism.”

USF co-investigators for the NICHD study include Tanya Murphy, MD, professor and Rothman Endowed Chair of Developmental Pediatrics in the Departments of Pediatrics and Psychiatry; and Adam Lewin, PhD, and Jane Mutch, PhD, both assistant professors of pediatrics.

- Story by Anne DeLotto Baier, USF Health Communications

A USF College of Public Health researcher has received a highly competitive National Institutes of Health grant to create and evaluate a web-based training program to help dentists and dental hygienists identify patients with eating disorders and refer them for treatment. Rita DeBate, PhD, associate professor in the Department of Community and Family Health, was awarded the two-year NIH Challenge Grant through the American Recovery and Reinvestment Act (ARRA). The ARRA funding is expected to be $985,517 over two years.

NIH AARA Challenge Grants were designed to spur new areas of research and trigger an influx of research dollars into communities across the nation starting in September 2009. With NIH receiving 20,000 challenge grant applications, competition was called “fierce.” While Florida universities received 177 awards through the ARRA, only a few were awarded in Florida.

Eating disorders, such as bulimia and anorexia nervosa, have potentially serious health consequences that can contribute to, or cause, death, according to the U.S. Center for Disease Control’s National Center for Health Statistics. Most people diagnosed with an eating disorder are under age 25, but deaths from eating disorders are highest among those between the ages of 25 and 64, NCHS statistics show.

Early identification, referral, and treatment significantly increase the likelihood of recovery, said Dr. DeBate. “Oral health providers play a fundamental role in the early detection, patient-specific oral treatment, and referral for care of eating disorders, because they are often the first health professionals to observe overt health effects. However, few dentists and dental hygienists are practicing this important clinical responsibility.”

Rita DeBate, PhD, received one of three highly competitive NIH ARRA Challenge Grants in Florida.

Over the two NIH-funded years, Dr. DeBate, the project’s principal investigator, and co-principal investigator Herbert Severson, PhD, senior research scientist at Oregon Research Institute, will customize their prototype web program, “Eating Disorders and Oral Health,” for use within dental and dental hygiene academic training programs. Adaptation of the prototype will be guided by input from dental and dental hygiene faculty and directors, an expert consultant panel, previous pilot data, and current e-learning methodology. Evaluation of the adapted web-based training program will involve 12 dental schools and dental hygiene programs across the country.

Damage to teeth, gums and oral tissue from disordered eating behaviors can begin as early as three months after excessive dieting or vomiting.

“The state of one’s oral health can be considered an early warning system for numerous health issues, including eating disorders,” Dr. DeBate said. “Consequently, oral health professionals can be among the first to observe the effects of eating disorders, but may not intervene for a variety of reasons. For instance, they may lack training and skill in identification of oral and physical symptoms of eating disorders, such as signs of malnutrition, dehydration and vomiting.”

Dr. DeBate’s previous research, which included focus groups with dentists and dental hygienists, revealed that they often felt uncomfortable approaching patients on sensitive topics such as an eating disorder.

“They realize that this is an important oral/systemic health issue, but also noted that they lacked confidence in patient approach, communication, and referral for treatment,” Dr. DeBate said. “In part, this program aims to improve skills in patient communication regarding this sensitive topic.”

Many dental health professionals also felt they could not start an oral treatment program with patients who, because of the secretive nature of their behavior, might be denying their eating disorder, she said. “Treatment can only begin when patients are ready for it. So assessing patient readiness to address disordered eating behaviors and secondary prevention are linked.”

Dr. DeBate and colleagues hope that the training program will increase dental professionals’ capacity to deliver eating disorder-specific secondary prevention and, ultimately, increase the rates of early treatment for people with eating disorders.

- Story by Randolph Fillmore, Florida Science Communications
- Photo by Eric Younghans, USF Health Communications

      Chances are, the federal government spends nearly twice as much on the Miami retiree as the Tampa one.

      Those are among the findings of a project called the Dartmouth Atlas, an ongoing examination of differences in health care spending around the U.S. On Friday, Jonathan Skinner, senior author of the Dartmouth Atlas John Sloan Dickey Third Century Chair of Economics at Dartmouth College, discussed those differences at a talk presented by the USF College of Public Health.

     Health economist Jonathan Skinner, PhD, chats with Donna Petersen, ScD, MHS, dean of the College of Public Health

       The nation’s most expensive Medicare patients are in Miami, where Medicare spends $16,351 per enrollee each year. Compare that to Tampa, where spending is $8,911 per enrollee.

      Those cost differences mount up, Dr. Skinner said.

      “You start ending up with enough money for, if not a new Ferrari, at least a used Ferrari,” he joked.

      The cost differences are particularly puzzling when you look at health quality measures , Dr. Skinner said. For example, Medicare spends far less per enrollee in San Francisco than in Miami.

     “Yet by all measures,” he said, “San Francisco is at least as good as Miami.”

      Those differences have important policy implications, Dr. Skinner said – both for reining in Medicare’s spiraling costs and for health care reform. What if we could deliver the same quality of care across the country on a San Francisco budget instead of a Miami one?

      “Could we get closer to universal coverage?” he asked.

      Dartmouth Atlas researchers have tried to find non-medical ways to explain the cost disparities. But possible differences in patients in different cities don’t seem to explain the gaps, Dr. Skinner said. Researchers have adjusted for differences in age, sex, race and income without explaining the disparities.

      What does have an effect? In some places, what Dr. Skinner describes as “entrepreneurial surgeons” – doctors who are aggressive adovocates for a particular procedure – can affect costs. Cardiologists in Elyria, Ohio, for instance, attracted national publicity after Dartmouth Atlas research showed that residents there were getting angioplasties at four times the national average.

      Similarly, another factor that explains regional differences is the amount of money each region spends on health care during the last two years of life -- how chronically ill patients are treated and how often they’re hospitalized.  Small differences in how doctors make decisions about whether to send a patient to a hospital or a specialist can add up to big changes in spending.

- Story by Lisa Greene, photos by Eric Younghans, USF Health Communications

Some of the USF Health faculty awarded federal research stimulus funds.

Since this spring, USF Health faculty submitted 116 proposals for economic stimulus funding available through the American Recovery and Reinvestment Act (ARRA). The ARRA applicants gathered Oct. 6 in the USF Health Rotunda to celebrate the fruits of their collaborative efforts – 21 federal research awards totaling more than $4.2 million.

The stimulus grants help support a wide variety of projects, from College of Medicine professor Gary Litman’s studies of the evolutionary origins of genes of immunity to College of Public Health researcher Rita DeBate’s work to create and evaluate a prototype web-based training program that will help dentists and dental assistants identify patients with eating disorders. Maureen Groer, director of the College of Nursing’s Center for Women’s Health Research, will use the award to supplement research examining the influence of breast feeding on postpartum stress and immunity.

Dr. Phil Marty spoke about research on the rise at USF.

“This was an opportunity in which faculty and staff from both sides of campus came together and put in tremendous time and energy needed to get a lot of excellent research proposals out the door quickly,” said Phillip J. Marty, PhD, associate vice president for the USF Health Office of Research. “Our efforts were successful.”

Stephen Klasko, MD, MBA, vice president for USF Health and dean of the College of Medicine, also thanked all who collaborated to submit proposals under a time crunch. “I’m proud of our faculty and appreciate very much all the hard work by the USF Health Research Office and Sponsored Research staff,” he said. “Even the grants we did not get have raised some opportunities for us.”

ARRA funds were dispersed from various institutes and centers across the National Institutes of Health (NIH) by Sept. 30 with the goal of moving the economy and stimulating jobs through research.

Dr. Stephen Klasko thanked all applicants and awardees for their hard work.

The reception recognizing ARRA applicants and awardees was part of ResearchONE, a week of events, Oct. 5-9, highlighting USF’s vast research enterprise and showcasing cutting-edge projects by both the campus community and the Tampa Bay region.

ResearchONE this year came on the heels of USF being named in The Chronicle of Higher Education as the fastest-growing university in the nation for federal research expenditures between 2000 and 2007. Simply translated, that means that during those seven years, no other group of faculty had a faster rate of earning new federal sponsorship for the discovery and creation of knowledge.

Research staff from USF Health and USF Sponsored Research worked with faculty to help get ARRA proposals out the door within a tight timeframe.

USF also recently announced a new record in research funding, $380.4 million in 2008-09 -- a $20 million increase over the previous year. USF Health’s colleges of medicine, nursing and public health attracted more than $232-million in research awards, or 61-percent of USF’s total awards.

For a full list of USF's NIH stimulus grant recipients (as of Oct. 2, 2009) compiled by the U.S. Department of Health and Human Services, click here.

L to R: Thomas Unnasch, PhD; who received ARRA awards supplementing his research with onchocerciasis and Eastern equine encephalitis, chats with Boo Kwa, PhD, and Matt Rollie of the Department of Global Health.

- Story by Anne DeLotto Baier, USF Health Communications
- Photos by Gil Williams, Gil Williams Photography

Dr. John Adams was recognized for the publication of “Comparative Genomics of the Neglected Human Parasite Plasmodium vivax Illuminates Malaria Parasite Biology” in the journal Nature and two articles in Public Library of Science Pathogens (PLoS Path). A member of the USF College of Public Health’s Global Health Infectious Diseases Research team, he studies protein ligands that help malaria parasites bind to a person’s red blood cell wall. His team uses advanced analytic technologies to pursue effective vaccine and mosquito-based therapies to prevent malaria caused by P. vivax and P. falciparum, the most common types of malaria. Dr. Adams contributed to a major international research initiative comparing the genome of the malaria parasite P. vivax with other sequenced Plasmodium genomes. Comparing similarities and differences between parasites’ genomes can help determine genetic targets for new drugs and vaccine development. Dr. Adams oversees the Vector-Borne Pathogen Laboratory, or insectary, where researchers study the complex life cycle of the malaria parasite transmitted by mosquitoes.

Dr. Russell Kirby was recognized for receiving the Godfrey P. Oakley, Jr. Award by the National Birth Defects Prevention Network for his significant contributions to the field of birth defects and his senior leadership in several collaborative research projects undertaken by the network. Dr. Kirby is a doctorally-trained geographer with extensive training and experience in public health practice, academic medicine and academic public health. While his research interests in maternal and child health are quite broad, he focuses on population-based research in birth defects and developmental disabilities epidemiology and prevention, as well as on risk factors for adverse pregnancy outcomes. He recently co-authored the book Perinatal Epidemiology for Public Health Practice, and collaborates extensively with professionals from a variety of disciplines, including medicine, nursing, public health, economics, sociology and psychology. Dr. Kirby is president of the Society for Pediatric and Perinatal Epidemiologic Research and of the Association of Teachers of Maternal and Child Health.

Dr. Hamisu Salihu was recognized for publication of a novel theory called “event memory hypothesis,” which suggests a possible molecular memory-recall programming pattern in human gestation using epidemiological and molecular evidence. The groundbreaking theory suggests that when fetal death occurs the event is retained (memorized) as a program that is replayed in future pregnancies. In 2008 this theory was published in the journals Medical Hypotheses and Obstetrics & Gynecology, and may help to understand and prevent the causes of fetal death. Dr. Salihu, director of the Center for Research and Evaluation at the Chiles Center for Healthy Mothers and Babies at USF, is a leading researcher in the field of infant mortality. He is a key player in the Black Infant Health Practice Initiative – a statewide collaborative to address the racial gap in infant deaths in Florida and to recommend policy changes at the local and state levels. He has authored more than 100 journal articles; including recently published studies that shed new light on obesity’s role in the black-white gap in infant mortality.

- Story by Anne DeLotto Baier, USF Health Communications
- Photos by Eric Younghans, USF Health Communications

USF Health neuroscientist Doug Shytle, PhD (right), accepts the Excellence in Innovation Award from Paul Sanberg, PhD, DSc, associate vice president for research and innovation.

The University of South Florida’s 2009 “Excellence in Innovation” award was presented last week to R. Douglas Shytle, PhD, associate professor and research scientist in the USF Center of Excellence for Aging and Brain Repair and the USF Silver Child Development Center. The award recognizes Dr. Shytle’s translational research achievements in developing new intellectual property based on clinical research and novel pharmacological discoveries which have led to newly commercialized therapeutics.

His most recent success is with a new experimental antidepressant, known as TC-5214, which is covered by USF patents and licensed to Targacept, Inc., a clinical-stage biopharmaceutical company that develops neuronal nicotinic receptor therapeutics. Targacept recently announced the positive results on TC-5214 as an augmentation treatment (add-on treatment) in a large clinical trial of adult patients with treatment resistant major depressive disorder.

While the Innovation Award encourages USF faculty to “think out of the professorial box,” for Dr. Shytle the road leading “out of the box” and to the success of TC-5214 was long, winding, and strewn with professional and emotional ups and downs as well as moments both serendipitous and Eureka.

“TC-5214 is a unique form of an old Merck drug called ‘mecamylamine,’ once used to treat severe hypertension in the 1950s,” explains Dr. Shytle. “Because later research suggested that mecamylamine interacted with brain nicotine receptors, we thought it might have a variety of therapeutic effects similar to nicotine, but without the side effects and addiction.”

Building on earlier USF clinical research using transdermal nicotine to treat patients with Tourette’s syndrome (characterized by body movements (tics) and vocalizations), Dr. Shytle, worked closely with USF professors, Archie A. Silver, MD, David Sheehan, MD, and Paul Sanberg, PhD, DSc, to investigate the effects of mecamylamine in Tourette's patients to see if it could help control their symptoms, as observed with nicotine.

“After carefully designing and conducting a large clinical trial in children with Tourette’s syndrome in 1999, we were shocked and disappointed to find that the drug had no effect on the tic symptoms,” recalls Shytle. “After reading several reports about how many antidepressants appeared to be interacting with nicotine receptors the same way as mecamylamine did, we decided to go back and take a second look at the data from our clinical trial. And there it was, like finding a gold nugget buried under the sand, clear evidence for an antidepressant effect of mecamylamine, but not for the placebo, in those Tourette’s subjects who had depressive symptoms.”

Based on those clinical findings, the researchers published a hypothesis paper in the prestigious journal, Molecular Psychiatry, proposing that nicotine receptor blockade might represent a novel pharmacological target for achieving therapeutic antidepressant properties. That hypothesis has now been supported by three clinical trials with mecamylamine, one by a group at Yale and two larger studies conducted by Targacept. The latest trial was conducted using TC-5214, a unique form of mecamylamine, predicted by the USF patents to be more effective with fewer side effects when compared to the older parent drug.

The results of this study are expected to have profound implications for the future treatment of major depression, making TC-5214’s impact on the market potentially huge.

“The Excellence in Innovation Award that Dr. Shytle received this year is a testament to the kind of creative translational research that attracts excellent industry partners, like Targacept, who have the vision and technical expertise to take our intellectual property to the next level of commercial development”, said Dr. Sanberg, associate vice president for research and innovation, who presented the award to Dr. Shytle Oct. 5 at USF's ResearchOne celebration. (Dr. Shytle was one of three USF faculty members who received the innovation award this year; the other two awardees were from Chemistry and Computer Science).

The USF license agreement with Targacept includes a percentage of sublicense and milestone payments as well as a royalty stream through 2021 should the drug achieve FDA approval.

"I am simply delighted that Dr. Shytle received this award for finding a 'diamond in the desert' after years of work," says Dr. Sheehan.

Dr. Shytle is an inventor on several USF patents in addition to four on mecamylamine and related compounds.

Story by Randolph Fillmore, Florida Science Communications
Photo by Joseph Gamble, USF Communications & Marketing

Cesar V. Borlongan, PhD, a neuroscientist at the University of South Florida Center for Aging and Brain Repair, worked with a team of researchers from Medical College of Georgia to test the treatment in laboratory experiments.

“To date, the thrombolytic agent tPA is the only effective drug for acute ischemic stroke; however, only about 2 percent of ischemic stroke patients benefit from this treatment due to its limited therapeutic window,” Borlongan said. “There is a desperate need to develop additional neuroprotective strategies. This research is an important step in rectifying the treatment issues, presenting a new, more effective treatment for stroke patients.”

USF neuroscientist Cesar Borlongan, PhD, was the study's principal investigator.

Stroke is the third leading cause of death in the United States, and currently accounts for almost 10 percent of deaths worldwide, claiming more lives than HIV/AIDS. During a stroke, a clot prevents blood flow to parts of the brain, which can have wide ranging short-term and long-term implications.

This study recorded the effect of intravenous minocycline in both isolated nerve cells and animal models after a stroke had been experimentally induced. At low doses the antibiotic was found to have a neuroprotective effect by rapidly reducing neuronal cell death (apoptosis) and alleviating behavioral deficits caused by stroke. The researchers also found that this neuroprotection was dose-dependent, underscoring the importance of the dose delivered for a safe outcome. While low-dose minocycline inhibited neuronal cell death at the early, or acute, phase of a stroke, a higher dose aggravated the brain injury from stroke.

An ongoing phase 1 clinical study funded by the National Institutes of Health is exploring the use of intravenous minocycline to treat acute ischemic stroke.

“The safety and therapeutic efficacy of low dose minocycline and its robust neuroprotective effects during acute ischemic stroke make it an appealing drug candidate for stroke therapy,” Dr. Borlongan said.

     The grant comes from the National Institutes of Health and is funded through the American Recovery and Reinvestment Act.

     The Nanomedicine Research Center’s  mission is to research areas of nanomedicine that ultimately could treat heart, lung and blood disorders. Research focuses closely on drug delivery and detection of disease cells, as well as integrating nanomedicine to tissue engineering and cell technologies.

     Nanomedicine uses extraordinarily tiny materials – too small to be seen with the naked eye -- to develop innovative ways to detect and treat disease. For example, a researcher might look for ways to use particles small enough to deliver drugs or therapeutic genes inside a tumor cell.

     Shyam Mohapatra, PhD, director of the Nanomedicine Research Center, is doing research using nanoparticles made of chitosan, a substance found in  shrimps, prawns and shellfish. His laboratory has shown that chitosan particles can safely and effectively deliver therapeutic genes into cells lining the lungs and effectively treat lung diseases such as  asthma or lung cancers in mice.

     Another project in the Nanomedicine Research Center has federal funding from the Office of Naval Research to develop ways to turn stem cells into blood cells.

     “In the battlefield, there’s never enough blood,” said Dr. Mohapatra. “This technology is very futuristic. It could lead to the development of devices that would be like a wristwatch with stem cells in it that could travel into your bloodstream and become blood cells” in case of injury.

     This grant, for a two-year period, will enable the Nanomedicine Center to hire one new faculty member and three support staff. Dr. Mohapatra, who also is the Mabel & Ellsworth Simmons Professor of Allergy & Immunology, expects the new personnel to add to the center’s ability to conduct interdisciplinary research between faculty in Medicine with those in basic sciences such as chemistry, physics, and biology and in engineering.

     -- Story by Lisa Greene, USF Health Communications

Chad Dickey's team at the USF Health Byrd Alzheimer's Institute focuses on manipulating with drugs or gene therapy the chaperone proteins that control the fate of the the Alzheimer's protein tau.

Tampa, FL (September 30, 2009) -- Inhibiting the protein Hsp70 rapidly reduces brain levels of tau, a protein associated with Alzheimer’s disease when it builds up abnormally inside nerve cells affecting memory, neuroscientists at the University of South Florida found. The study is reported online today in the Journal of Neuroscience.

“Now that we’ve discovered that targeting the chaperone protein Hsp70 can clear tau, it could be helpful in finding more effective drugs for Alzheimer’s disease,” said the study’s senior author Chad Dickey, PhD, assistant professor of molecular medicine who works out of the Byrd Alzheimer’s Institute at USF Health “The therapeutic strategy may also be applicable to other neurodegenerative diseases involving Hsp70, such as Huntington disease, Amyotrophic lateral sclerosis (ALS), and some cancers.”

Hsp70 is a one of several “chaperone” proteins that supervises the activity of tau inside nerve cells. The normal function of tau is to support the structure of nerve cells, much like the skeleton provides a scaffold to support the body. Tau is inside nerve cells, while another hallmark protein associated with Alzheimer’s, beta amyloid, is outside the neurons.

Working with researchers at the University of Michigan, the USF team tested the effects of several compounds on Hsp70 in cell models and brain tissue from mice genetically modified to develop the memory-choking tau tangles. Some compounds activated Hsp70, and others were Hsp70-inhibitors.

One of the more effective Hsp70-inhibitor drugs the researchers discovered was a derivative of methylthioninium chloride, or Rember™, the first experimental medication reported to directly attack the tau tangles in patients with Alzheimer’s disease. Rember™ was heralded as a major development in the fight against Alzheimer’s when results in early clinical trials were announced last year at the International Conference on Alzheimer’s disease.

“But Rember™ and its derivatives do have some inherent problems; they’re not very potent so effective therapy would require fairly high doses, Dickey said.

“The drug does help prevent the protein (tau) from clumping together, but that in itself doesn’t mean it’s actively getting rid of the toxic tau,” he said. “Now that we know Hsp70 is a target of Rember™, we can develop similarly-acting drugs that will more specifically target this chaperone protein in affected areas of the brain, resulting in fewer side effects.”

The USF researchers originally thought activating Hsp70 would direct the chaperone protein to decrease the tau gone bad -- preventing tau from stacking up into tangles inside cells involved in memory and destroying them. But instead of restoring tau to its normal supportive function, activating Hsp70 actually led to tau’s preservation and even more accumulation, Dickey said. “Basically we think the chaperone binds to the tau, and somehow in the process of trying to fix things decides to keep holding onto tau when it shouldn’t. So, activating Hsp70 is not necessarily what we want to do; we ultimately want to inhibit Hsp70 to promote the release or clearance of tau …to kill the bad tau.”

Dr. Dickey emphasizes that problems with Hsp70 alone do not cause Alzheimer’s. It likely develops from a convergence of various factors in the brain, he said, including deposits of the other featured Alzheimer’s protein beta amyloid, or a genetic defect; disruption of cell signaling; a breakdown in the neuron’s support structure, and then accumulation of tau into the memory-choking tangles.

Dr. Dickey’s team at USF focuses on how to manipulate with drugs or gene therapy the chaperone proteins that regulate tau’s fate – determining whether it’s preserved or cleared from the brain. The University of Michigan team works on identifying and developing compounds that may be effective against Alzheimer’s disease and other tauopathies.

The study was supported by the national Alzheimer’s Association, the National Institute on Aging, the Abe and Irene Pollin Fund for CBD Research from CurePSP: The Society for Progressive Supranuclear Palsy, and the National Institute of Neurological Disorders and Stroke.

The study’s other authors were Umesh Jinwal (lead author), Yoshinari Miyata, John Koren III, Jeffrey Jones, Justin Trotter, Lyra Chang, John O’Leary, David Morgan, Daniel Lee, Cody Shults, Aikaterini Rousaki, Edwin Weeber, Erik Zuiderweg, and Jason Gestwicki.

- USF Health -

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.health.usf.edu

Timothy Bender and Desiree Del Orbe are among the USF undergraduate students learning about the ecology of Eastern equine encephalitis with the help of Hassan K. Hassan, MSc (center), a research associate in Dr. Thomas Unnasch's laboratory.

While we spent the summer and entered the fall abuzz over the potential for H1N1 virus, or the ‘Swine Flu,’ to sweep the nation, some University of South Florida students and one high school student found employment that put them in search of mosquitoes carrying a rarer but deadlier virus, Eastern equine encephalitis, or EEE.

“Eastern equine encephalitis is rare, but when humans get the disease the fatality rate is 50 to 70 percent,” says Thomas Unnasch, PhD, a professor in the USF Department of Global Health, College of Public Health. “It is nearly 100 percent fatal for horses. The ecology of EEE in the Southeastern United States is not well understood.”

Beneficiaries of NIH stimulus funding

Dr. Unnasch, who has had ongoing funding from the National Institutes of Health to study the ecology and transmission of EEE and several other diseases, received additional funding under the “American Recovery and Reinvestment Act of 2009” which allocated $21 million nationally over two years for educational supplements to existing research programs. The stimulus funding has provided extended summer employment for more than 3,000 undergraduates and high school students nation-wide.

With his supplemental grant, Dr. Unnasch was able to hire six USF undergraduates and one high school student to take an active role in tracking down which of the 60-plus varieties of mosquitoes in the Tampa Bay area carry EEE. In addition, his collaborators at Auburn University were also able to hire student summer researchers.

The goal of the research is to identify the vectors (the mosquitoes) carrying the EEE virus and identify their feeding sources. Some EEE carrying mosquitoes feed exclusively on birds, says Dr. Unnasch, while others may feed on mammals of several varieties. Because of suburban development, mosquitoes carrying EEE may be coming into closer contact with people, especially in rapidly developing areas such as Hillsborough and Pasco Counties, where USF undergraduate student Timothy Bender and Raphael Shattenkirk, a student at Tampa Preparatory School, trap mosquitoes several days a week.

“Raphael sets the traps in the evening and I pick them up in the morning,” explains Bender, a biology major.

Mosquitoes caught in netted traps left overnight in developing areas of Hillsborough and Pasco counties are frozen and brought to the laboratory for analysis under the microscope. The researchers want to identify the mosquitoes carrying EEE and their feeding sources.

The traps attract mosquitoes using a small light bulb, the release of carbon dioxide from dry ice left overnight, and a small fan that sucks them into the netted traps. In the morning, Bender pops the trap bag in the freezer, which kills them, and then he delivers them to the USF lab where USF undergraduate student Desiree Del Orbe puts the dead mosquitoes, up to 60-100 per day, under the microscope and sorts them by sex, species, and which of the females (the only mosquitoes that bite) have had a recent “blood meal,” evidenced by their swollen bellies. These are the mosquitoes of interest, the ones that may be carrying EEE.

“Ultimately, we want to determine which mosquitoes carry the virus, the source of their blood meals, and the ecological area where the mosquitoes were active,” says Del Orbe. “This information will help the counties with mosquito spraying when they can target specific areas.”

According to Dr. Unnasch, Florida spends $75 million annually on mosquito control, but the efforts are not as efficiently targeted as they could be if we understood more about the ecology of the virus.

Hands-on Research Experience

Students in the lab, under the supervision of Hassan K. Hassan, MSc, research associate, run a battery of tests, including real-time Polymerase Chain Reaction (PCR) to look for virus RNA, and DNAPCR tests on the blood meal to determine meal source. Their results are shared with both the state Department of Health and the county mosquito control offices. In this win-win summer research project not only do the counties get good data, but students learn the research process from field to bench.

“They get to learn about lab safety,” says Hassan. “They learn why we use this chemical or that one, they learn to use the lab equipment and how to avoid sample contamination. Many students would not learn these things until graduate school.”

Christy Ottendorfer, PhD, a post-doctoral fellow in the lab, says that 2009 has been a “big year” for EEE because of the rainfall amounts and the increased mosquito populations. “Fortunately there have been no human cases, but Florida is leading the nation in equine deaths from EEE,” says Dr. Ottendorfer.

There is a “known unknown” in EEE research. The big issue for the research team is to find what they call the “bridge species” of mosquito. “If mosquitoes carrying the virus feed on birds and non-human mammals, how do people get it?” asks Ottendorfer.

According to Dr. Unnasch, the student researchers are indispensable.

“The real hard part of this research is getting people out there to do the field work, the sample collections,” he says. “It helps to have a bunch of enthusiastic people willing to get out there to set the traps and collect samples. Their help has allowed us to increase the number of collection sites.”

The other benefit to having student help is that with an increase in good data, the NIH is more likely to continue funding the project. The stimulus funding runs through Oct. 31, and then many of the students will continue to work on the project as volunteers, says Hassan.

- Story and photos by Randolph Fillmore, Florida Science Communications

The five-year grant from the National Institute on Aging was awarded to Jun Tan, MD, PhD, Robert A. Silver Chair and Director of the Rashid Laboratory for Developmental Neurobiology at the Silver Child Development Center, USF Department of Psychiatry. The study co-investigators are Paul Sanberg, PhD, DSc, director of the Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, and David Morgan, PhD, professor in the Department of Molecular Pharmacology and Physiology and chief scientific officer of the Byrd Alzheimer Institute at USF Health.

Recent USF studies have shown that immunity can be transferred using human umbilical cord blood cells, which improves the pathology associated with Alzheimer’s disease in a mouse model. Other studies have demonstrated that a specific immune system suppression is correlated with significantly reduced abnormal levels of the beta amyloid protein linked to Alzheimer’s disease.

“This new NIH study will continue to build on our understanding of the HUCBC’s mechanism behind improvement in Alzheimer’s disease,” Dr. Tan said. “It will help provide a better understanding of brain immune cells called microglia, which promote brain inflammation in Alzheimer’s disease.”

Dr. Tan and his colleagues previously demonstrated that once a specific molecule, CD40, on the surface of these microglia cells becomes activated by its partner, CD40L (CD40 ligand), the scene is set for a cascade of events leading to brain inflammation that injures the brain’s neurons. They also showed that the trigger for this harmful immune response can be blocked by specific antibodies.

In this study, Dr. Tan and his team plan to test the hypothesis that HUCBC could reduce the interaction between the CD40L molecule and its CD40 target, which in turn would decrease Alzheimer’s pathology in the brain. The experiments will be performed on (transgenic) mice genetically modified to develop memory problems mimicking Alzheimer’s disease as they age.

Furthermore, the researchers plan to create a cocktail combining the precise molecules they believe are the key players behind HUCBC’s beneficial effects. “We will give the compound to these transgenic mice to assess the possibility of bypassing the need for HUCBC and making future therapies more cost effective,” Dr. Tan said.

"This approach shifts the focus from treating symptoms of Alzheimer's disease to treatments that slow down the disease or prevent it altogether.” Dr. Tan said. “Our long-term goal is to move this combination treatment into phase I human trials for patients with mild to moderate Alzheimer’s disease.”

    Ataxia patients Avery Zaritsky, Kyle Bryant and Nygel Lanz spoke at USF Health last week about the need for more research into Friedreich's and other ataxias.

     Just a few years ago, living with ataxia was so much lonelier.

     Avery Zaritsky was diagnosed with the disease at 19. For a long time, she and her husband, Paul, felt it was, at least medically, them against the world. Doctors even told them not to have children.

     "Eight or nine years ago, we were all on our own," said Dr. Paul Zaritsky, a Tampa dentist. "Now we have hundreds of scientists backing us up."

     Patients and researchers voiced that same sense of optimism repeatedly at USF at how rapidly research into Friedreich's and other ataxias has started to show promise. USF hosted a series of events last week that will benefit the USF Ataxia Research Center and FARA, the Friedreich's Ataxia Research Alliance.

     Friedreich's is a rare neuromuscular disorder which affects the body's ability to balance, as well as causing muscle weakness and other problems. There is no known treatment or cure.

     But just in the last five years, a host of promising research avenues have blossomed, said Jennifer Farmer, executive director of FARA, at a research symposium last week. Just since 2004, research has gone from three different avenues of attack to nine, she pointed out.

     "This is why we're so excited," she said. "We need multiple shots on goal."

     Among those shots is research by Dr. Theresa Zesiewicz, professor of neurology and director of the USF Ataxia Research Center. Dr. Zesiewicz is studying how the smoking cessation drug varenicline could be used as a treatment to help ataxia patients with balance difficulties.

     Dr. Zesiewicz wowed last week's crowd when she showed videos showing patients with limited balance and substantial difficulty walking before taking varenicline and notable improvements afterwards. She cautioned that those results are preliminary and that the drug has substantial side effects.

     Still, such efforts are among those that give Farmer hope.

     "I like to think of the last decade as the decade of progress," she said.

     Dr. Stephen K. Klasko, dean of the USF College of Medicine and CEO of USF Health, told the group that research is nearing the final step.

      "We know a lot about this disease," he said. "What we don't know yet is how to stop it."

      Dr. Stephen Klasko, dean of the USF College of Medicine, talks about USF's ataxia research.

     But that day will come, he said.

      "Thank you for your courage and your patience," Dr. Klasko said to the ataxia patients present. "We will beat this."

        That can't happen soon enough for patients like Kyle Bryant, who was diagnosed with Friedreich's ataxia at age 17.

"I think Friedreich's ataxia gives us all a sense of urgency," Bryant said. "I don't know where I will be in the next five years. I will never be as able as I am now."

Jennifer Farmer, executive director of FARA; Dr. Theresa Zesiewicz, director of the USF Ataxia Research Center; Dr. Clifton Gooch, USF neurology chair; Dr. Jeffrey Krischer, director of the USF Pediatrics Epidemiology Center and principal investigator of the NIH-funded Rare Diseases Clinical Research Network Data Management and Coordination Center

     Yet Bryant already had to give up bicycling, switching to a recumbent trike that is easier to balance on. He's made the most of that: in 2006, he founded a group called Ride Ataxia, a group that has biked 3,300 in the last two years, helping raise $700,000 for ataxia research.

"We were totally devastated in the beginning," Bryant said at USF last week. "We've taken an amazing journey and turned 180 degrees, and experienced some amazing things that we wouldn't have otherwise."

Still, Bryant feels time is short.

"We need to do it fast," he told the audience at last week's symposium. "We need to do it hard. We need to do it now."

-- Story by Lisa Greene, USF Health Communications; Video by Anne DeLotto Baier, USF Health Communications; Photos by Eric Younghans, USF Health Communications

RELATED STORIES:
- Energizing Research for a Cure
- From wheelchair to walking, ataxia patient finds hope through USF study

The Florida Chapter of ACC held its annual meeting the weekend of Aug. 22 and, as part of the meeting, internal medicine residents and cardiology fellows from throughout Florida were invited to submit their research to compete for the group’s Young Investigator Award.

Of the 20 abstracts submitted from around the state (five of which were from USF) three were chosen to make oral presentations. Of those select three (two of which were from USF), one went on to be the overall winner and earn the Young Investigator Award: USF’s Dr. Reynolds.

Third-year cardiology resident Christopher Reynolds wins at ACC meeting.

Dr. Reynolds, a third-year USF internal medicine resident who will be starting a cardiology fellowship at USF next July, earned the award for his research work titled “Can Heart Failure Medications Prevent Trastuzumab-Induced Cardiotoxicity?” The win also earned him a plaque and $500 cash, recognition at the American College of Cardiology’s president’s banquet Aug. 22, and reimbursement for his travel costs and registration fees for the meeting paid.

Also earning an invitation to make an oral presentation was Swathy Kolli, a USF cardiology fellow. Dr. Kolli’s work was titled “Determinants of Pulmonary Hypertension in Young Adults.”

The oral presentations were given before the full conference assembly and judged by a panel of cardiologists.

Mentoring both Drs. Kolli and Reynolds was Maya Guglin, MD, PhD, associate professor and director of the USF Heart Failure program.

“We competed with all Florida medical schools, including the traditionally leading University of Florida and University of Miami,” Dr. Guglin said.

“But when I came to Orlando it was USF all over. Three out of six posters were from us, and two out of three oral presentations were ours as well. Just one year ago only one fellow, Rias Ali, participated in this competition. I am very pleased to say that almost all studies we brought to Orlando are going to be presented at national and international levels. Dr. Swathy Kolli is presenting our findings on pulmonary hypertension in young adults at the American Heart Association scientific sessions – this is one of the two largest cardiology annual meetings in the world. Drs. Christopher Reynolds, Catherine Law, and Charles Glover are going to Boston in September to Heart Failure Society of America meeting. This is an achievement. This means that our findings are recognized as important well beyond regional level.”

In addition to Drs. Kolli and Reynolds, four other USF residents and fellows had their abstracts accepted for the ACC competition. The other four were: Drs. Rias Ali, Charles Glover, Catherine Law, and Hammad Khan.

“We are thrilled,” said Anne B. Curtis, MD, professor and director of the USF Division of Cardiology.  “USF dominated in both oral and poster sessions at the meeting. Thank you to all the fellows who participated and thank you to all the faculty mentors for the research projects. Finally, thank you to Dr. Maya Guglin for coordinating the research efforts of our fellows. We are very pleased to see the increasing participation by all the fellows in scholarly activity. It will enhance their cardiology fellowship experience immensely, and it will increase the recognition of our program regionally and nationally.”

Story by Sarah A. Worth, USF Health Communications

Tampa, FL -- An upcoming  symposium at USF Health will bring together scientists, clinicians and patients to discuss promising new research for Friedreich’s ataxia and other ataxias, a group of degenerative diseases of the nervous system that adversely affect balance, coordination and movement.

“Understanding Energy for a Cure” will be held 6:15 to 8 p.m. on Thursday, August 27, in Room 1013 at the Morsani Center for Advanced Healthcare at USF Health, 13330 USF Laurel Drive, Tampa, FL 33612. The symposium, sponsored by the Friedreich’s Ataxia Research Alliance (FARA) and the USF Ataxia Research Center (ARC), is free and open to the public.

Dr. Jeffrey Krischer, professor and director of the USF Pediatrics Epidemiology Center, will speak on “The Challenges and Promise of Rare Diseases Research.”  Dr. Krischer is the principal investigator for a major National Institutes of Health data coordinating center that supports the Rare Diseases Clinical Research Network, which is addressing the complexities of diagnosing and treating a variety of rare diseases, including ataxias.

Other speakers will be Dr. Theresa Zesiewicz, professor of neurology and director of the USF ARC; Jennifer Farmer, executive director of FARA; and Ron Bartek, president and founder of FARA.  Topics will cover new research, the care and management of ataxia, with an emphasis on Friedreich’s; and patient advocacy. Dr. Stephen Klasko, CEO for USF Health and dean of the College of Medicine, will moderate a panel discussion on the patient’s perspective of ataxia.

“Research investigating the underlying molecular mechanisms of Friedreich’s and spinocerebellar ataxia may lead not only to treatments for ataxias, but also to more effective therapies for imbalance caused by stroke, tumors and toxins,” Dr. Zesiewicz said.

The USF ARC provides care for patients suffering from imbalance and ataxia, while conducting both basic science and patient-oriented research.  The center has a special focus on Friedrich’s ataxia, a debilitating neuromuscular disease that typically strikes children and teenagers and leaves them wheelchair bound by their early 20s.

The center is currently spearheading several clinical trials in Friedreich’s and spinocerebellar ataxias, partnering with other universities and national organizations, including FARA, the National Ataxia Foundation and the Bobby Allison Ataxia Research Alliance, to bring promising medications to human testing.

For more information, please call (813) 974-5909.

About USF Health
USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

About FARA
The Friedreich's Ataxia Research Alliance's (FARA) mission is to marshal and focus the resources and relationships needed to cure FA by raising funds for research, promoting public awareness, and aligning scientists, patients, clinicians, government agencies, pharmaceutical companies and other organizations dedicated to curing FA and related diseases.

Tampa, FL (Aug. 11, 2009) -- A 65-year-old women goes into the hospital for routine hip surgery. Six months later, she develops memory loss and is later diagnosed with Alzheimer’s Disease. Just a coincidence? Researchers at the University of South Florida and Vanderbilt University don’t think so. They suspect that the culprit precipitating Alzheimer’s disease in the elderly women may be a routine administration of high concentrations of oxygen for several hours during, or following, surgery – a hypothesis borne out in a recent animal model study.

Dr. Gary Arendash of the Florida Alzheimer’s Disease Research Center at USF and Dr. L. Jackson Roberts II at Vanderbilt University used mice genetically altered to develop abnormal levels of the protein beta amyloid, which deposits in the brain as plaques and eventually leads to Alzheimer’s-like memory loss as the mice age. They found that young adult Alzheimer’s mice exposed to 100-percent oxygen during several 3-hour sessions demonstrated substantial memory loss not otherwise present at their age. Young adult Alzheimer’s mice exposed to normal air had no measurable memory loss, and neither did normal mice without any genetic predisposition for Alzheimer’s disease.

The authors suggest that people genetically predisposed to Alzheimer’s disease or with excessive amounts of beta amyloid in their brains are at increased risk of developing the disease earlier if they receive high concentrations of oxygen, known as hyperoxia. Their study is published online this month in NeuroReport.

“Although oxygen treatment beneficially increases the oxygen content of blood during or after major surgery, it also has several negative effects that we believe may trigger Alzheimer’s symptoms in those destined to develop the disease,” said USF neuroscientist Arendash, the study’s lead author. “Our study suggests that the combination of brain beta amyloid and exposure to high concentrations of oxygen provides a perfect storm for speeding up the onset of memory loss associated with Alzheimer’s Disease.”

USF neuroscientist Gary Arendash was the study's lead author.

While postoperative confusion and memory problems are common and usually transient in elderly patients following surgery, some patients develop permanent Alzheimer’s-like cognitive impairment that remains unexplained. Recent studies have indicated that general anesthesia administered during surgery may increase a patient’s risk of Alzheimer’s disease, but the laboratory studies did not use animals or people predisposed to develop the disease.

“Postoperative memory loss can be a fairly common and devastatingly irreversible problem in the elderly after major surgical procedures,” said Roberts, an MD who holds an endowed chair in Pharmacology at Vanderbilt University School of Medicine. “There has been much speculation as to the cause of this memory loss, but the bottom line is that no one really knows why it happens. If all it takes to prevent this is reducing the exposure of patients to unnecessarily high concentrations of oxygen in the operating room, this would be a major contribution to geriatric medicine.”

The USF-Vanderbilt study looked at 11 young adult mice genetically modified to develop memory problems as they aged, mimicking Alzheimer’s disease. After behavioral tests confirmed the mice had not yet developed memory impairment at age 3 months – about age 40 in human years – the researchers exposed half the Alzheimer’s mice to 100-percent oxygen for three hours, three times over the next several months. The protocol was intended to replicate initial and supplemental exposures of elderly patients in hospital operating rooms and recovery suites to high concentrations of oxygen. The other half of the mice were exposed to 21-percent oxygen, the concentration of oxygen in typical room air.

When researchers retested the mice after the final gas exposure, they found that Alzheimer’s mice exposed to 100-percent oxygen performed much worse on tests measuring their memory and thinking skills than the Alzheimer’s mice exposed to normal room air. In fact, the Alzheimer’s mice exposed to room air demonstrated no memory loss. Moreover, exposure of young adult mice without beta amyloid protein deposited in their brains to 100-percent oxygen did not adversely affect their memories. This is consistent with studies in humans showing that exposure of young adults to high concentrations of oxygen has no harmful effects on memory.

The researchers also demonstrated that even a single 3-hour exposure to 100-percent oxygen caused memory deficits in the Alzheimer’s mice. Furthermore, when they examined the brains of these mice, they found dramatic increases in levels of isofurans, products of oxygen-induced damage from toxic free radicals. The increase was not present in the brains of normal control mice exposed to the single hyperoxia treatment.

How might high concentrations of oxygen hasten memory impairment in those destined to develop Alzheimer’s disease? The researchers suggest the striking increase of isofurans during surgery may be one triggering mechanism, particularly in cardiac bypass surgery where very high blood oxygen levels are routinely attained and permanent memory loss often occurs months after the surgery. Secondly, exposure to high oxygen concentrations prompts abnormal swelling of brain cell terminals that transmit chemical messages from one brain cell to another and may further disrupt already frayed nerve cell connections in those at risk for Alzheimer’s. Third, high concentrations of oxygen combined with beta amyloid plaques constricts blood vessels and decreases blood flow to the brain more than either one alone.

The authors caution that the study in mice may or may not accurately reflect the effects of hyperoxia in human surgery patients.

“Nonetheless, our results call into question the wide use of unnecessarily high concentrations of oxygen during and/or following major surgery in the elderly,” Roberts said. “These oxygen concentrations often far exceed that required to maintain normal hemoglobin saturation in elderly patients undergoing surgery”.

Arendash published initial evidence in 1987 that Alzheimer’s disease starts in the brain several decades before memory loss occurs. His research focuses on developing promising therapeutics in Alzheimer’s mice that can quickly be transferred to human clinical trials. Roberts, an expert on the role of free radicals and oxidative injury in disease, has discovered novel products of free radical damage that may be associated with several age-related brain dysfunctions. Also participating in the hyperoxia study were Dr. Takashi Mori of Saitama Medical University (Japan) and Dr. Kenneth Hensley of the Oklahoma Medical Research Foundation.

The study was supported by grants within the Florida Alzheimer’s Disease Research Center, a statewide project sponsored by the National Institute on Aging, and a National Institutes of Health Merit Award to Dr. Roberts.

An estimated 10 million baby boomers will develop Alzheimer's disease in their lifetime. The disease usually begins after age 60, and risk rises with aging. The direct and indirect cost of Alzheimer's disease in the United States is a staggering $150 billion a year, according to the national Alzheimer’s Association.

- USF Health -
USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

- Vanderbilt University Medical Center -
Vanderbilt Medical Center (VMC) is a comprehensive healthcare facility dedicated to patient care, research, and biomedical education. Its reputation for excellence in each of these areas has made Vanderbilt a major patient referral center for the Mid-South. Each year, people throughout Tennessee and the Southeast choose Vanderbilt for their health care needs, not only because of its excellence in medical science, but also because the faculty and staff are dedicated to treating patients with dignity and compassion. Vanderbilt's mission is to advance health and wellness through preeminent programs in patient care, education, and research.

The newly formed USF Academy of Inventors is the brainchild of Paul Sanberg, PhD, DSc, USF’s associate vice president for Research & Innovation and the holder of 28 U.S. patents, including the first patents for using bone marrow and cord blood as a source of neural stem cells for brain repair.

“Inventors embody the creativity and innovation which is a hallmark of a fast-growing research university,” said Dr. Sanberg, director of the Center of Excellence for Aging and Brain Repair at USF Health. “I wanted to increase the perception at the university that innovation and patents are important, leading to transfer of technology to our society.”

For more about the academy, and it's charter class, click here.

July 20, 2009 -- Results of a new study published online this week in the Proceedings of the National Academy of Sciences question the long-term effects of transplanted cells in the brains of patients suffering from Huntington’s disease. The study, conducted by Dr. Francesca Cicchetti of Laval University in Québec, Canada, Dr. Thomas B. Freeman of the University of South Florida (USF) Department of Neurosurgery and Brain Repair, Tampa, FL, and colleagues provides the first demonstration that transplanted cells fail to offer a long-term replacement for degenerating neurons in patients with Huntington’s disease.

Huntington’s disease is a neurodegenerative disease of genetic origin that targets a particular type of neuron. The loss of these neurons is responsible for the appearance of involuntary movements as well as cognitive and psychiatric impairments. Over a decade ago, USF neurosurgeon Dr. Freeman initiated a clinical trial of neural cell transplantation in patients with Huntington’s disease in an attempt to alleviate the devastating symptoms that characterize this disease.

Some patients demonstrated some mild, transient clinical benefits that lasted for about two years. However, the loss of functional recovery after this time indicated that graft survival and functionality may be jeopardized long-term.

Study senior co-author Dr. Thomas Freeman, a professor in the USF Department of Neurosurgery and Brain Repair, is a leader in stem cell transplantation research for neurodegenerative disorders.

The post-mortem study of three cases described in PNAS is the first demonstration that 1) graft survival is indeed attenuated long-term, 2) the grafts undergo degeneration that resembles the pathology observed in Huntington’s disease, and 3) the brain’s inflammatory response could contribute to the compromised survival of grafted cells. The authors also demonstrated that cortical neurons develop Huntington’s disease synapse on the grafts, and may cause neurotoxicity to the healthy cells, inducing grafted neuronal cell death.

Last year, researchers at Rush University Medical Center, USF, and Mount Sinai School of Medicine published research in Nature Medicine showing that grafts in patients with Parkinson’s disease develop Lewy bodies -- a marker of Parkinson’s disease -- after 14 years. Those patients benefited from the grafts for about 12 years, and only about 5 to 8 percent of the transplanted cells had this finding.

“This latest study shows that grafts in patients with Huntington’s disease also undergo disease-specific neuronal degeneration,” said USF's Dr. Freeman, a senior co-author of the study. “However, the neural degeneration in the (genetically unrelated) grafts was even more severe than what was observed in the patient’s own brain. Additionally, clinical benefit, if any, only lasted about two years. These findings may be important to future therapeutic trials of stem cells for the treatment of Parkinson’s and Huntington’s diseases.”

Despite the excitement for cell transplantation therapy using embryonic or stem cells, these results raise concerns for the therapeutic potential of transplantation as a treatment option for Huntington’s disease, the study authors report. However, these observations suggest new potential mechanisms involved in the development of the disease, they conclude. A more in-depth investigation could allow the development of novel therapeutic strategies. The control of the patient’s immune and inflammatory responses holds therapeutic potential and Dr. Cicchetti and colleagues continue their research in that direction.

Dr. Francesca Cicchetti is a professor at the Department of Psychiatry/Neuroscience at Laval University and a researcher in neurobiology. She directs a research laboratory, which focuses on the understanding of neuronal degeneration and the development of treatment strategies for neurodegenerative diseases.

Dr. Thomas B. Freeman is a USF neurosurgeon at Tampa General Hospital, and director of clinical research and medical director of the Center of Excellence for Aging and Brain Repair at the University of South Florida.

This work includes the scientific contribution of the following authors: Samuel Saporta (USF Department of Neurosurgery and Brain Repair), Robert Hauser (Parkinson's Disease and Movement Disorders National Parkinson's Foundation Center of Excellence, USF), Martin Parent (Groupe de recherche sur le système nerveux central (GRSNC)), Martine Saint-Pierre (Centre de Recherche du CHUL (CHUQ)), Paul Sanberg (USF Department of Neurosurgery and Brain Repair), Xiao Li (Emory University School of Medicine), John Parker (University of Louisville Health Sciences Center), Yaping Chu (Rush University Medical Center), Elliot Mufson (Rush University Medical Center), and Jeffrey Kordower (Rush University Medical Center).

Tampa, FL (July 6, 2009) -- Coffee drinkers may have another reason to pour that extra cup. When aged mice bred to develop symptoms of Alzheimer’s disease were given caffeine – the equivalent of five cups of coffee a day – their memory impairment was reversed, report University of South Florida researchers at the Florida Alzheimer’s Disease Research Center.

Back-to-back studies published online today in the Journal of Alzheimer’s Disease show caffeine significantly decreased abnormal levels of the protein linked to Alzheimer’s disease, both in the brains and in the blood of mice exhibiting symptoms of the disease. Both studies build upon previous research by the Florida ADRC group showing that caffeine in early adulthood prevented the onset of memory problems in mice bred to develop Alzheimer’s symptoms in old age.

“The new findings provide evidence that caffeine could be a viable ‘treatment’ for established Alzheimer’s disease, and not simply a protective strategy,” said lead author Gary Arendash, PhD, a USF neuroscientist with the Florida ADRC. “That’s important because caffeine is a safe drug for most people, it easily enters the brain, and it appears to directly affect the disease process.”

USF neuroscientist Gary Arendash, PhD, says the preclinical findings suggest caffeine could be a viable treatment for established Alzheimer's.

Based on these promising findings in mice, researchers at the Florida ADRC and Byrd Alzheimer’s Center at USF hope to begin human trials to evaluate whether caffeine can benefit people with mild cognitive impairment or early Alzheimer’s disease, said Huntington Potter, PhD, director of the Florida ADRC and an investigator for the caffeine studies. The research group has already determined that caffeine administered to elderly humans without dementia quickly affects their blood levels of β-amyloid, just as it did in the Alzheimer’s mice.

“These are some of the most promising Alzheimer’s mouse experiments ever done showing that caffeine rapidly reduces beta amyloid protein in the blood, an effect that is mirrored in the brain, and this reduction is linked to cognitive benefit,” Potter said. “Our goal is to obtain the funding needed to translate the therapeutic discoveries in mice into well-designed clinical trials.”

Arendash and his colleagues became interested in caffeine’s potential for treating Alzheimer’s several years ago, after a Portuguese study reported that people with Alzheimer’s had consumed less caffeine over the last 20 years than people without the neurodegenerative disease. Since then, several uncontrolled clinical studies have reported moderate caffeine consumption may protect against memory decline during normal aging. The highly controlled studies using Alzheimer’s mice allowed researchers to isolate the effects of caffeine on memory from other lifestyle factors such as diet and exercise, Arendash said.

Huntington Potter, PhD, director of the Florida Alzheimer's Disease Research Center, says the Byrd Alzheimer's Center at USF hopes to begin clinical trials testing caffeine treatment in people with mild cognitive impairment or early Alzheimer's.

The just-published Florida ADRC study included 55 mice genetically altered to develop memory problems mimicking Alzheimer’s disease as they aged. After behavioral tests confirmed the mice were exhibiting signs of memory impairment at age 18 to 19 months – about age 70 in human years – the researchers gave half the mice caffeine in their drinking water. The other half got plain water.

The Alzheimer’s mice received the equivalent of five 8-oz. cups of regular coffee a day. That’s the same amount of caffeine – 500 milligrams -- as contained in two cups of specialty coffees like Starbucks, or 14 cups of tea, or 20 soft drinks.

At the end of the two-month study, the caffeinated mice performed much better on tests measuring their memory and thinking skills. In fact, their memories were identical to normal aged mice without dementia. The Alzheimer’s mice drinking plain water continued to do poorly on the tests.

Caffeine treatment removed beta amyloid plaques from the brains of the Alzheimer’s mice.

In addition, the brains of the caffeinated mice showed nearly a 50-percent reduction in levels of beta amyloid, a substance forming the sticky clumps of plaques that are a hallmark of Alzheimer’s disease. Other experiments by the same investigators indicate that caffeine appears to restore memory by reducing both enzymes needed to produce beta amyloid. The researchers also suggest that caffeine suppresses inflammatory changes in the brain that lead to an overabundance of beta amyloid.

Since caffeine improved the memory of mice with pre-existing Alzheimer’s, the researchers were curious to know if it might further boost the memory of non-demented (normal) mice administered caffeine from young adulthood through old age. It did not. Control mice given regular drinking water throughout their lives performed as well on behavioral tests in old age as normal mice who received long-term caffeine treatment, Arendash said. “This suggests that caffeine will not increase memory performance above normal levels. Rather, it appears to benefit those destined to develop Alzheimer’s disease.”

Caffeinated Alzheimer's mice performed much better on tests measuring their memory and thinking skills, like finding the submerged platform (circled in photo) in this water maze. Their memories were the same as normal aged mice without dementia.

The researchers do not know if an amount lower than the 500 mg. daily caffeine intake received by the Alzheimer’s mice would be effective, Arendash said. For most individuals, however, this moderate level of caffeine intake poses no adverse health effects, according to both the National Research Council and the National Academy of Sciences. Nonetheless, Arendash said, individuals with high blood pressure or those who are pregnant should limit their daily caffeine intake.

If larger, more rigorous clinical studies confirm that caffeine staves off Alzheimer’s in humans, as it does in mice, this benefit would be substantial, Arendash said. Alzheimer’s disease attacks nearly half of Americans age 85 and older, and Alzheimer’s and other dementias triple healthcare costs for those age 65 and older, according to the Alzheimer’s Association.

In addition to the Florida ADRC, Byrd Alzheimer’s Center and Eric Pfeiffer Suncoast Alzheimer’s and Gerontology Center at USF, researchers from the Bay Pines VA Healthcare System; Saitama Medical University, Saitama, Japan; and Washington University School of Medicine, St. Louis, collaborated on the research. The studies were supported by grants to investigators in the Florida ADRC, a statewide project sponsored by the National Institute on Aging and housed at the University of South Florida’s Byrd Alzheimer’s Center.

Chuanhai Cao, PhD, was lead author of the paper reporting caffeine reduces beta amyloid in the brains and blood of Alzheimer's mice.

Journal articles cited:

1. Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer’s Disease Mice; Gary W Arendash, Takashi Mori, Chuanhai Cao, Malgorzata Mamcarz, Melissa Runfeldt, Alexander Dickson, Kavon Rezai-Zadeh, Jun Tan, Bruce A Citron, Xiaoyang Lin, Valentina Echeverria, and Huntington Potter; Journal of Alzheimer’s Disease, Volume 17:3 (July 2009).

2. Caffeine Suppresses Amyloid-β Levels in Plasma and Brain of Alzheimer’s Disease Transgenic Mice; Chuanhai Cao, John R Cirrito, Xiaoyang Lin, Lilly Wang, Deborah K Verges, Alexander Dickson, Malgorzata Mamcarz, Chi Zhang, Takashi Mori, Gary W Arendash, David M Holzman, and Huntington Potter; Journal of Alzheimer’s Disease, Volume 17:3 (July 2009).

- About USF Health -

USF Health (www.health.usf.edu) is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

- About the Journal of Alzheimer’s Disease -

The Journal of Alzheimer's Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 5.101 according to Thomson Reuters' 2008 Journal Citation Reports. The Journal is published by IOS Press (http://www.iospress.nl).

Tampa, FL (July 1, 2009) -- A human growth factor that stimulates blood stem cells to proliferate in the bone marrow reverses memory impairment in mice genetically altered to develop Alzheimer’s disease, researchers at the University of South Florida and James A. Haley Hospital found. The granulocyte-colony stimulating factor (GCSF) significantly reduced levels of the brain-clogging protein beta amyloid deposited in excess in the brains of the Alzheimer’s mice, increased the production of new neurons and promoted nerve cell connections.

The findings were reported online in Neuroscience earlier this month and will appear in the journal’s print edition in August.

GCSF is a blood stem cell growth factor or hormone routinely administered to cancer patients whose blood stem cells and white blood cells have been depleted following chemotherapy or radiation. GCSF stimulates the bone marrow to produce more white blood cells needed to fight infection. It is also used to boost the numbers of stem cells circulating in the blood of donors before the cells are harvested for bone marrow transplants. Advanced clinical trials are now investigating the effectiveness of GCSF to treat stroke, and the compound was safe and well tolerated in early clinical studies of ischemic stroke patients.

“GCSF has been used and studied clinically for a long time, but we’re the first group to apply it to Alzheimer’s disease,” said USF neuroscientist Juan Sanchez-Ramos, MD, PhD, the study’s lead author. “This growth factor could potentially provide a powerful new therapy for Alzheimer’s disease – one that may actually reverse disease, not just alleviate symptoms like currently available drugs.”

Microglia (in green) attack the beta amyloid deposits (red) in GCSF-treated Alzheimer's mice.

The researchers showed that injections under the skin of filgrastim (Neupogen®) -- one of three commercially available GCSF compounds -- mobilized blood stem cells in the bone marrow and neural stem cells within the brain and both of these actions led to improved memory and learning behavior in the Alzheimer’s mice. “The beauty in this less invasive approach is that it obviates the need for neurosurgery to transplant stem cells into the brain,” Dr. Sanchez-Ramos said.

Based on the promising findings in mice, the Alzheimer’s Drug Discovery Foundation is funding a pilot clinical trial at USF’s Byrd Alzheimer’s Center. The randomized, controlled trial, led by Dr. Sanchez-Ramos and Dr. Ashok Raj, will test the safety and effectiveness of filgrastim in 12 patients with mild to moderate Alzheimer’s disease

The researchers worked with 52 elderly mice, equivalent to the human ages of 60 to 80 years. About half (24) were mice genetically altered to develop symptoms mimicking Alzheimer’s disease by the time they reach 5-months old. The others (28 normal, or non-Alzheimer’s, mice) were not. The researchers confirmed through a series of tests that the Alzheimer’s mice were memory impaired before beginning the experiments.

Some mice were treated for three weeks with injections of the GCSF compound filgrastim. At the end of study, the Alzheimer’s mice treated with GCSF demonstrated clearly improved memory, performing as well on behavioral tests as their non-Alzheimer’s counterparts. The Alzheimer’s mice administered saline injections instead of GCSF continued to perform poorly. GCSF treatment did not boost the already excellent memory performance demonstrated by the non-Alzheimer’s mice tested before the study began.

Based on the promising findings in mice, Dr. Juan Sanchez-Ramos and Dr. Ashok Raj will lead a pilot clinical trial at the USF Byrd Center testing GCSF (filgrastim) in patients with mild to moderate Alzheimer's disease.

Further experiments showed that the size and extent of beta amyloid deposited in the brains of the Alzheimer’s mice was significantly less in those treated with GCSF. Depending on their ages, mice treated with GCSF had a 36 to 42-percent reduction in beta amyloid, the protein considered a major culprit in the development of Alzheimer’s disease.

GCSF reduced the burden of beta amyloid deposited in the brains of the Alzheimer’s mice by several means, the researchers found. One was by recruiting reinforcements to clear beta amyloid accumulating abnormally in the brain. The growth factor prodded bone-marrow derived microglia outside the brain to join forces with the brain’s already-activated microglia in eliminating the Alzheimer’s protein from the brain. Microglia are brain cells that act as the central nervous system’s main form of immune defense. Like molecular “Pac-men,” they rush to the defense of damaged or inflamed areas to gobble up toxic substances.

The growth factor also appeared to increase the production of new neurons in the area of the brain (hippocampus) associated with memory decline in Alzheimer’s disease and to form new neural connections.

“The concept of using GCSF to harness bone marrow-derived cells for Alzheimer’s therapy is exciting and the findings in mice are promising, but we still need to prove that this works in humans” said Dr. Raj, a physician researcher at the Byrd Alzheimer’s Center at USF Health.

In addition to Dr. Sanchez-Ramos, other authors of the Neuroscience paper were Shijie Song, PhD; Vasyl Sava, PhD; Briony Catlow, PhD; Xiaoyang Lin; Takashi Mori, PhD; Chuanhai Cao, PhD; and Gary Arendash, PhD. The study was funded by grants from the Alzehimer's Drug Discovery Foundation, Helen Ellis Foundation, Florida Alzheimer's Disease Research Center, and the Byrd Alzheimer's Center at USF.

- USF Health -

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

- Photo by Eric Younghans, USF Health Communications

L to R: Dr. Jorge Marcet, director of the Division of Colorectal Surgery, with general surgery residents Dr. Beth Krieger (1st place research award) and Abhishek Mathur (3rd place) at the American College of Surgeons Florida Chapter annual scientific meeting.

Two USF surgery residents were among the three winners of a high-profile research presentation last month at the Florida Chapter of the American College of Surgeons 2009 Scientific Annual Meeting in Palm Coast, FL.

Beth Krieger, MD, who is completing a one-year research fellowship in the Division of Colorectal Surgery, won first place in the Florida ACS “Edward M. Copeland Annual Paper Competition” for her research paper titled “Long-term Results of Transanal Excision for Locally Advanced Rectal Cancer Following Neoadjuvant Therapy.” The retrospective study found that transanal excision is an effective alternative to radical surgery for select patients with advanced lower rectal cancer who have complete disappearance of their cancer following preoperative chemotherapy and radiation. Krieger, who will be a fourth-year general surgery resident in July, received a $1,000 award.

Abhishek Mathur, MD, a first-year general surgery resident, won third place for his paper titled “Site of Recurrence after Pancreatectomy for Pancreatic Adenocarcinoma Is Not Influenced by Margin Status or Adjuvant Chemoradiotherapy, But Can Impact Survival.” He received a $250 award.

Dr. Krieger and Dr. Mathur were among 10 residents from medical schools across Florida invited to present the findings of their research papers at the chapter’s annual scientific meeting. The winning papers were selected from among more than 60 submitted by residents in surgical specialties.

The annual Edward Copeland competition focuses on resident research related to clinical surgery outcomes. Originality and applicability of research to practice are among the criteria for the award.

- Newsbrief by Anne DeLotto Baier, USF Health Communications

MRSA infections that are transmitted from dogs and cats to their human handlers, and vice-versa, are increasing—with infections of the skin, soft-tissue, and surgical infections the most common.

MRSA, or methicillin-resistant Staphylococcus aureus, is a term often used to describe staph infections that are resistant to antibiotics. This and other bite-related and septic syndromes caused by cats and dogs are discussed in a Review in the July 2009 edition of The Lancet Infectious Diseases, written by Dr. Richard Oehler and colleagues at the USF College of Medicine and James A. Haley Veterans' Hospital.

In the United States, dog and cat bites make up roughly 1 percent of emergency room visits yearly, with similar numbers reported in Europe. Women and the elderly are most at risk of being bitten by a cat. Men in general and those younger than 20 of both sexes are most likely to be injured. Most bite exposures occur in young children, involve unrestrained dogs on the owner’s property, and about 20 percent involve a non-neutered dog.

Risk is highest in young boys ages 5 to 9, because of their small size and lack of understanding of provocative behaviour, the authors write. Children, due to their small height, often receive bites to the face, neck, or head. Adults are most frequently bitten on the hand, followed by face, scalp, neck, thigh or leg.

Proper treatment of dog and cat bites should involve treatment of the immediate injury (whether superficial or deep) and then management of the risk of acute infection, including washing with high pressure saline if possible, and antibiotics in selected cases.

Severe infections can develop in about 20 percent of all cases, and are caused by Pasteurella, Streptococcus, Fusobacterium, and Capnocytophaga bacteria from the animal’s mouth, plus possibly other pathogens from the human’s skin. In countries with endemic rabies, rabies prophylaxis should be considered.

Sepsis can be a severe complication of bite wounds, particularly those infected with C canimorsus, P multocida, Staphylococcus spp (including MRSA), and Streptococcus spp. Meningitis, endocarditis, and peritonitis can also complicate bite-wound infections. Several other species, including Bacteroides, Fusobacterium, Neisseria, and Prevotella, might also produce bite-wound sepsis in individuals with leukaemia and lupus, and in those receiving chronic steroids.

As community-acquired strains of MRSA increase in prevalence, a growing body of clinical evidence has documented MRSA colonization in domestic animals, often implying direct acquisition of S aureus infection from their human owners. MRSA colonization has been documented in companion animals such as horses, dogs, and cats, and these animals have been viewed as potential reservoirs of infection.

MRSA-related skin infections of pets seem to occur in several manifestations, including simple dermatitis, and even perineal cellulitis, and can be easily spread to owners. Some people carry MRSA germs in their noses or on their skin without realizing it, but the bacteria do not cause infection unless they enter the body -- through a bite or open wound, for instance.

Specific therapy for pet-associated MRSA infections is similar to regimens used in most community-acquired MRSA syndromes. “Much more remains to be learned about MRSA and pet-associated human infections," the authors write.

“Pet owners are often unaware of the potential for transmission of life-threatening pathogens from their canine and feline companions. Bite injuries are a major cause of injury in the USA and Europe each year, particularly in children. Bites to the hands, forearms, neck, and head have the potential for the highest morbidity," they conclude.

"Health-care providers are at the forefront of protecting the vital relationships between people and their pets. Clinicians must continue to promote loving pet ownership, take an adequate pet history, and be aware that associated diseases are preventable via recognition, education, and simple precautions.”

Other USF/VA authors of the The Lancet Infectious Diseases review were Dr. Sandra Gompf, Dr. Ana Velez, and Dr. Jorge Lamarche.

- Source: Press Release from The Lance Infectious Diseases

Tampa, FL (June 17, 2009) -- Using an opioid drug to induce hibernation in rats reduces the damage caused by an artificial stroke, reports a study published today in the open access journal BMC Biology. Researchers found that those animals put into a chemical slumber -- a hibernation-like state that cooled their brains -- suffered less behavioral impairment after a period of cerebral artery blockage than control rats.

Cesar Borlongan, PhD, a neuroscientist at the University of South Florida Center for Aging and Brain Repair in Tampa, FL, worked with a team of researchers from the National Institutes of Health, to investigate the role of the opioid system in brain injury and protection.

“Studies in hibernating and active squirrels have shown that ‘natural hibernation’ has anti-ischemic effects – protecting against the formation of blood clots. We’ve shown that a drug that induces hibernation can achieve similar results in the brain,” Borlongan said. “Even a small decrease in the brain’s temperature appears to be neuroprotective.”

Borlongan and his colleagues dosed the rats intravenously with [D-ala2,D-leU5]enkephalin (DADLE), a drug from the same pharmaceutical family as morphine and heroin. DADLE is used to cryogenically preserve donated organs to keep them viable for transplantation. The researchers found that, after an experimental stroke, the pre-treated animals performed better than control rats in a series of behavioral tests. DADLE significantly reduced the size of the stroke, and prevented cell death processes and behavioral abnormalities.

“The observation that this substance, previously shown to induce hibernation, improves recovery from cerebral ischemia means it could provide a new pharmacological treatment for stroke,” Borlongan said.

During ischemic stroke, diminished blood flow and oxygen trigger a cascade of events that may cause additional, delayed damage to brain cells. DADLE helped the stroke-damaged area of the brain survive this assault, Borlongan said. More studies, including injection of the drug following a stroke, are needed to determine exactly how the drug works. But Borlongan suggests that it may promote proliferation of the body’s own natural stem cells, which then migrate from bloodstream to the brain to control and repair damage.

- USF Health -

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.health.usf.edu

- BMC Biology -

BMC Biology - the flagship biology journal of the BMC series - publishes research and methodology articles of special importance and broad interest in any area of biology and biomedical sciences. BMC Biology (ISSN 1741-7007) is covered by PubMed, MEDLINE, BIOSIS, CAS, Scopus, EMBASE, Zoological Record, Thomson Reuters (ISI) and Google Scholar.

RELATED STORY:
USF neuroscientist advances stem cell therapy for stroke

- The Lancet Lifeline Interview with Dr. Borlongan

Neuroscientist Cesar Borlongan, PhD, a leading stem cell researcher, has returned to USF where his career began.

Cesar Borlongan has come full circle – back to the University of South Florida College of Medicine, where he began his neurosciences career as a postdoctoral fellow and aspiring stem cell researcher 16 years ago. This fall he joined the USF Center of Excellence for Aging and Brain Repair, where he is a professor and vice chair of research for the Department of Neurosurgery and Brain Repair.

In the interim, Dr. Borlongan was a senior staff fellow at the National Institute of Health’s National Institute on Drug Abuse, where he earned awards for outstanding scientific achievement and research excellence. The distinguished NIH tenure was followed by six years at Medical College of Georgia, where he directed the Institute of Molecular Medicine and the Department of Neurology Cell Transplantation.

“We are fortunate that a neuroscientist of Dr. Borlongan’s caliber has returned to USF,” said Paul R. Sanberg, PhD, DSc, distinguished professor of neurosurgery and director of the Center for Aging and Brain Repair. “He is one of the pioneers in cell therapy research for stroke and has been instrumental in advocating the consistent, rigorous design of preclinical studies so that findings can be readily translated to stroke treatment.”

Throughout his career Dr. Borlongan has focused on advancing stem cell therapy for brain disorders, particularly adult stroke and neonatal stroke. At the Center for Aging and Brain Repair, he works alongside other leading neuroscientists exploring the potential of neural cells and alternatives to embryonic stem cells (including adult bone marrow cells and cord blood cells) as treatments for brain injury and neurological diseases like Parkinson’s, Huntington’s, Alzheimer’s, stroke and ALS.

Dr. Borlongan brought a team of four postdoctoral fellows and a faculty member as well as a five-year NIH grant totaling more than $3.5 million to USF from Medical College of Georgia. He is working with USF Health neurosurgeons and neurologists and researchers at the Byrd Alzheimer’s Center to develop innovative treatments for stroke using stem cells. In particular, he is exploring ways to harness stem cells produced by the body’s own bone marrow – known as endogenous stem cells -- to repair or prevent brain damage from stroke.

If even small numbers of these outlying stem cells in the bloodstream could be coaxed to proliferate with growth factors or drugs and honed to the stroke-damaged area of the brain, the potential benefits could be substantial, Dr. Borlongan said. Because the cells originate in the person being treated, they would be recognized as “self” by the body and not trigger a potentially dangerous immune response.

“One of the major obstacles to cell transplantation has been graft rejection. When you introduce stem cells from a donor to a transplant recipient, the graft can always be rejected as a foreign substance. The patient can suffer infection and other adverse side effects,” Dr. Borlongan said. “But these problems, including the need for powerful immunosuppressants following transplantation, could be circumvented by using stem cells that come from the patient.”

Dr. Borlongan (above) brought $3.5-million NIH grant and a team of researchers with him to the USF Center for Aging and Brain Repair, including postdoctoral fellow SeongJin You, PhD (below).

“We’ve learned a lot in the last decade,” said Dr. Borlongan said. “I’m more optimistic than ever that we’ve jumped through the scientific hurdles needed to demonstrate the safety and effectiveness of stem cell therapy in animal models. We know what works in mice – but now we have to apply it to humans!”

Dr. Sanberg and Dr. Borlongan at USF, working with colleagues at the University of Pennsylvania, laid the foundation for the world’s first experimental procedure to repair brain damage in stroke patients. In 1998, surgeons at the University of Pittsburgh implanted human neurons derived from a tumor and rendered benign (hNT-neurons) into the brain of a patient who suffered a stroke the year before. The clinical trial was built in part on USF research showing that the hNT-neurons restored the movement of rats subjected to experimental stroke.

Since then, only a few small clinical trials of cell therapy for stroke have been reported. While there have been no complications directly related to the stem or progenitor cells, evidence about the cells’ effectiveness in restoring function in patients is still lacking.

Many rodent studies have demonstrated that stem cell transplantation -- by surgery, direct injections to the brain and less invasive IV infusion, can improve stroke recovery. But, the underlying reasons for the success of these therapies remain largely unknown. The researchers use various strains of rodents and stroke models; they implant, infuse and inject different cell types; they put the cells in different target locations in the brain and employ different behavior tests to assess functional recovery. All these variables, without standardized treatment protocols and outcome measures, make it difficult to compare studies and determine the best conditions for cell therapy following a stroke, Dr. Borlongan said.

Dr. Borlongan is investigating how the body's own bone marrow-derived stem cells (glowing in center of screen) could be prodded to rescue stroke-damaged regions of the brain.

In an editorial published last year in the journal Regenerative Medicine, Dr. Borlongan called for academia, industry, the NIH and the FDA to adopt translational research guidelines that would promote more consistency in designing preclinical studies and help advance cell therapy for stroke from laboratory to clinic.

“It is imperative for clinical translation that these cells be tested in multiple models of focal stroke, in both genders and in multiple laboratories,” he wrote.

- Story by Anne DeLotto Baier, USF Health Communications
- Photos by Eric Younghans, USF Health Communications

RELATED STORIES:
- Opioid-induced hibernation protects against stroke

- The Lancet Lifeline Interview with Dr. Borlongan

Dr. Jamie Winderbaum Fernandez, a psychiatrist, will investigate cellular mechanisms of Alzheimer’s disease with the aim of developing treatments to help rid the brain of memory-robbing toxins. Dr. Celso Silva, an obstetrician-gynecologist, wants to know whether a non-invasive test to measure the length of chromosomes tips could predict the success of in vitro fertilization among women experiencing infertility. Dr. Xiaohong Zhang, a molecular biologist, hopes to pinpoint an enzyme inhibitor that could help ovarian cancer patients overcome resistance to chemotherapy.

While their scholarly interests and backgrounds are diverse, the three newest members of USF Health’s K-30 Scholars in Patient-Oriented Research Program (K30 Scholars Program) are all excited about the prospect of learning new skills to help advance their research careers.

K30 Scholarship Boost from Dean

They are recipients of the first K30 Program Dean’s Faculty Scholar Awards in Clinical and Translational Research to support junior faculty members participating in the two-year research career development program. Stephen Klasko, MD, MBA, CEO for USF Health and dean of the College of Medicine, and Patricia Emmanuel, MD, Associate Dean for Clinical Research, have designated $60,000 for each of the three scholars to help subsidize departmental salaries to the faculty members while they dedicate three-quarters of their time to research.

“We are committed to growing our own talented clinical and translational investigators -- faculty who are passionate about tackling intellectual challenges and creating new knowledge that will lead to better products and therapies for patients,” said Ken Zuckerman, MD, co-director of the K30 Scholars Program for USF Health. “This program is considered so crucial to the future of USF Health research efforts that Drs. Klasko, (Phil) Marty and Emmanuel have extended the commitment to provide similar salary support for up to four faculty members a year, on a competitive basis.”

Growing Our Own

The K30 Scholars Program began at USF Health in 2005 with the support of a National Institutes of Health Clinical Research Curriculum Award. It is preparing the next generation of clinical researchers by arming them with critical skills needed to accelerate medical discoveries to improve health. When the new class begins this July, 22 junior faculty and senior subspecialty fellows will have been enrolled in the highly competitive program, which leads to a Master’s of Science in Medical Sciences degree with a concentration in clinical and translational research. Drs. Fernandez, Silva and Zhang will join a diverse contingent of scholars from interdisciplinary oncology, obstetrics and gynecology, pathology, pediatrics, physical therapy, psychiatry, nursing and surgery.

The K30 scholars complete a rigorous curriculum that includes courses in ethical and regulatory aspects of clinical research, cultural and diversity issues, epidemiology, biostatistics, and science communication. They learn the nuts and bolts of how to do competitive research, something not typically taught during medical school or residency training. The scholars prepare and critique grant applications and design, conduct and analyze clinical trials and translational studies. They hear from faculty at different stages of their academic research careers and learn practical strategies to help them map out successful careers in patient-oriented research.

“One of the things we did not anticipate and of which we are most proud,” Dr. Zuckerman said, “is how easily these scholars from such diverse areas of interest and expertise have interacted and contributed to each others’ research and career development – essential skills for becoming critical members of interdisciplinary research teams that will drive scientific discovery in the 21st century.”

Jumpstarting Research Careers

K30 Scholars Program graduate Brian Giunta, MD, MS

The intense training pays off. Brian Giunta, MD, MS, a graduate of the inaugural class of K30 scholars, was awarded a prestigious four-year $629,500 Mentored Clinical Scientist Development Award from NIH even before completing the program last year. Dr. Giunta continues to work with his mentor USF neuroscientist Jun Tan, MD, PhD, and colleagues out of the neuroimmunology laboratories in the Department of Psychiatry. Using a mouse-model for HIV-induced Alzheimer’s disease, they are investigating whether flavonoids -- natural substances found in citrus, dark berries, green tea and red wine -- may protect the brain against dementia. Dr. Giunta has been promoted from instructor to assistant professor and is working toward a PhD degree. The talented young translational scientist has recently published two peer-reviewed papers directly related to his grant as lead author, and others are in the pipeline.

“I never would have been able to jumpstart my research career without having a portion of my time blocked out to participate in the K30 Scholars Program,” Dr. Giunta said.

Information about the three inaugural K30 Scholar Program scholarship recipients follows:

Jamie Winderbaum Fernandez, MD

Dr. Fernandez is an instructor in the Department of Psychiatry and Behavioral Medicine and attending physician at Tampa General Hospital. While a medical student at Cornell University, she won a spot in the highly selective Howard Hughes Medical Institute-National Institutes of Health Research Scholars (Cloister) Program. She spent two years at the NIH campus in Bethesda, MD, conducting mentored research in lipid signaling and defects in cellular trafficking associated with Lowe syndrome, a rare genetic disorder that causes physical and mental disabilities and medical problems.

Dr. Fernandez completed a residency in adult psychiatry at Stanford University before joining USF this year. She is interested in geriatric psychiatry and neurodegenerative diseases like Alzheimer’s. For her K30 research project she plans to examine the role of amyloid precursor protein (APP) in the accumulation and clearance of Alzheimer’s plaques in the brain.

“There seems to be a huge push now for neuroscience research. It’s an area of medicine that for years remained largely unstudied,” Dr. Fernandez said. “With recent advances in laboratory techniques, animal models, vaccine-mediated approaches and neuroimaging, there is hope that we’ll be able to broaden our understanding of the brain and brain disease.”

“For Alzheimer’s disease, studies are suggesting that catching the disease early, even before symptoms are apparent, will be important for effective treatment… otherwise, it’s like trying to treat diabetes after medical complications have already occurred.”

Dr. Fernandez’s K30 Scholar mentor will be Jun Tan, MD, PhD, the Silver Endowed Chair in Developmental Neurobiology at USF Health.

Celso Silva, MD

Dr. Silva is an assistant professor in the Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility. He earned his MD degree in Brazil and completed a residency in obstetrics and gynecology at Brown University and a fellowship in reproductive endocrinology and infertility at the University of Pennsylvania. His postgraduate research in reproductive medicine was supported by the National Institutes of Health (NIH) Research Training Program.

From the laboratory to the clinic, Dr. Silva focuses on the issue of aging and fertility – specifically the ability of stem cells to generate the oocytes (eggs) that decrease dramatically in numbers and/or quality among older women. For his K30 research project, he plans to study the effectiveness of several ways --including testing blood and the fluid inside ovarian follicles – to measure the protective tips on the ends of chromosomes known as telomeres. Shortened telomeres have been implicated in age-related decline in the developmental potential of eggs. Working with the USF IVF research team, he hopes to validate a diagnostic test to measure telomeres, and determine whether telomere length actually predicts which women are more likely to conceive an IVF baby before patients commit to the demanding treatment regimen.

The best translational research is a two-way street, not just a bench-to-bedside enterprise, Dr. Silva said. “It goes beyond applying knowledge gained from basic science studies to the care of patients. Before you can develop viable diagnostic tools and treatments, you need to bring observations and insights from day-to-day clinical experiences back to the laboratory to re-evaluate and enhance your original findings,” he said.

“This approach requires a multidisciplinary team where there is constant dialogue between clinicians and basic scientists.”

Dr. Silva appreciates having more time to devote to research. “For clinicians in academic medicine and teaching hospitals, the pressures to see more patients and educate students and residents can be tremendous,” he said. “To promote the development of translational research you really need to be somewhat shielded from other activities… The K30 program accommodates that.”

Dr. Silva’s K-30 mentor will be David Keefe, MD, chair of Obstetrics and Gynecology.

Xiaohong (Mary) Zhang, PhD

Dr. Zhang is an assistant professor in the Department of Pathology and Cell Biology. She holds a PhD in molecular biology from the University of Texas, M.D. Anderson Cancer Center, and completed a postdoctoral fellowship in molecular oncology at Moffitt Cancer Center.

Dr. Zhang is looking forward to interacting with other K30 scholars who bring different perspectives to the table.

“Good research requires thinking outside the box, and that means it’s important to communicate and collaborate with researchers outside your field,” she said. “I strongly believe the K30 Scholars Program will be a great opportunity to enhance my career as an ovarian cancer researcher. I want to bridge my basic science knowledge about histone deacetylases to help clinicians restore chemotherapy sensitivity in patients with ovarian cancer.”

Dr. Zhang’s K-30 mentors will be Santo Nicosia, MD, chair of Pathology and Cell Biology, and Jonathan Lancaster, MD, PhD, associate professor of Oncologic Sciences and director of the Center for Women’s Oncology at Moffitt Cancer Center.

For more information on the K30 Scholars in Patient Oriented Research Program, contact Sandy Anderson at sanders2@health.usf.edu, or visit http://health.usf.edu/research/k30/

- Story by Anne DeLotto Baier, USF Health Communications
- Photos by Eric Younghans and Klaus Herdocia, USF Health Communications

A new clinical study, sponsored by the Friedreich’s Ataxia Research Alliance (FARA), will investigate whether varenicline (Chantix®) improves neurological symptoms that can lead to frequent falls in patients with FA. Chantix® is approved by the U.S. Food and Drug Administration to help cigarette smokers stop smoking. Currently, there is no effective treatment for FA. The double blind, randomized, placebo-controlled pilot study will be led by principal investigator Dr.Theresa Zesiewicz, professor of neurology at the University of South Florida College of Medicine, and co-investigator Dr. David Lynch, associate professor of neurology and pediatrics at Children’s Hospital of Philadelphia.

Dr. Zesiewicz noticed that the uncoordinated movements (ataxia) and balance problems of a patient with fragile X tremor /ataxia syndrome improved greatly after he started varenicline in an attempt to quit smoking. The symptoms worsened when the medication was discontinued. Dr. Zesiewicz found similar results when treating patients with other types of ataxia, and several of her case reports were published last year in medical journals.

“Our preliminary findings with varenicline in ataxia patients provided information that warrants further formal clinical research. Varenicline has a possible novel mechanism of action in the nervous system that we were unaware of,” said Dr. Zesiewicz, who developed a protocol for the clinical trial and applied to FARA for funding.

The pilot study aims to determine whether the findings Dr. Zesiewicz observed in a few ataxia patients can be replicated in a larger group of adults diagnosed with FA.

Chantix®, a Pfizer drug, acts at sites in the brain affected by nicotine. “We do not completely understand how Chantix® may be working to improve symptoms of ataxia, however it is clearly different from the other agents under development for FA,” Dr. Lynch said. “If Chantix does prove beneficial, it would offer a complementary approach for treating FA.”

The researchers do not recommend that those with FA or other types of ataxia begin off-label use of Chantix®, which requires a prescription. Clinical trials are needed to determine the effectiveness, proper dose and potential side effects of Chantix® in this population, they say.

“This is the first clinical trial that FARA has supported through a research grant. We are grateful to our talented team of investigators who have moved quickly to bring this discovery to FA patients in an organized and rigorous study and to the Pfizer corporation for providing the drug for this study,” said FARA Executive Director Jennifer Farmer.

“Clinical studies are needed to determine the risks and benefits of a drug. In such cases where the drug has been approved for another indication, all too often proper trials do not occur and patients are taking risks with a drug without understanding the real potential benefit.”

For more information on this study – “Double-Blind, Randomized, Placebo-Controlled Pilot Study of Varenicline in the Treatment of Friedreich’s Ataxia” -- go to www.curefa.org/registry and select Clinical Trials or visit www.clinicaltrials.gov and search for “Friedreich’s ataxia”.

About FA
FA is a degenerative, neuromuscular disease that gradually robs patients of their ability to walk, compromises speech, hearing, and vision, and often comes with complications of serious diabetes and heart disease. Although rare, FA is the most prevalent inherited ataxia, affecting about one in every 50,000 people in the United States.

About FARA
The Friedreich's Ataxia Research Alliance's (FARA’s) mission is to marshal and focus the resources and relationships needed to cure FA by raising funds for research, promoting public awareness, and aligning scientists, patients, clinicians, government agencies, pharmaceutical companies and other organizations dedicated to curing FA and related diseases. For more information, go to www.CureFA.org.