//www.youtube.com/watch?v=8EGW58Uq-Yk

Patients have always been the center of the yearly scientific symposium hosted by the Friedreich’s Ataxia Research Alliance (FARA) and the University of South Florida Ataxia Research Center.

But, for the 8^th annual symposium held Sept. 15 at USF’s Gibbons Alumni Center, patients took on an even more prominent role. The panel discussion in which they share their stories about living with the rare, but devastating, progressive neurodegenerative disease, including patient participation in clinical trials, was moved up in the program format.

The 8th annual scientific symposium hosted by FARA and USF was held in the USF Gibbons Alumni Center.  More than 750 in the FA community listened to the latest perspectives on ataxia research from patients and scientists, in person and internationally via live-stream.

And this year, led by FARA spokesperson Kyle Bryant as moderator, the four patient panelists were the ones driving the conversation with leading researchers from academia and industry who sat onstage beside these young adults to discuss the latest advances in the search for effective treatments and, ultimately, a cure.

More than 250 attendees gathered at the USF Gibbons Alumni Center for the symposium, which was also live-streamed and viewed worldwide by those in the FA community, over 500 people in eight countries. The symposium “Understanding Energy for a Cure” kicked off a series of events in Tampa Bay to raise awareness about FA, culminating Sept. 17 with the FARA Energy Ball gala, which this year raised $2 million to benefit innovative ataxia research.

The patient panel, moderated by FARA spokesperson Kyle Bryant (far left), helped drive the conversation with leading researchers. Participants were, from left, Alex Fielding, Sean Baumstark, Alison Avery and Anna Gordon.

“My parents and sister never really let me believe that Friedreich’s ataxia was going to stop me,” said panelist Alison Avery, 22, diagnosed with Friedreich’s ataxia at age 18, who is interning with the National Football League’s social responsibility department in NYC following college graduation. “It may have changed the way that I do certain things, but right now I’m living on my own in New York City, and that’s something not everyone would do, whether or not they have FA.”

Alison participates in the “Cardiac MRI and Biomarkers in Friedreich’s Ataxia” study at Children’s Hospital of Philadelphia and another evaluating the relationship between exercise performance and neurological/cardiac status and overall functioning in children and adults with FA. “I’m excited to be able to share my perspective on being involved in different research studies,” she said. “I feel like that’s something more people should know, especially the researchers — about how patients actually feel about trials and studies.”

USF System President Judy Genshaft said USF has made neurosciences, including ataxia research, a high institutional research priority.

Friedreich’s ataxia typically strikes in childhood or adolescence and leads to a progressive loss of coordination and muscle strength, eventually robbing young people of their energy and ability to walk. While the neurological symptoms are most visible, FA is a multisystem disease that can adversely affect cardiac function, metabolism, vision, hearing and the skeletal system. There is currently no approved treatment for FA.

“Throughout the history of this event, the one constant has been how incredibly motivating and inspiring it is to hear from patients and their families who never fail to share one valuable message: ‘Live life to its fullest despite the challenges of Friedreich’s ataxia,’” said USF System President Judy Genshaft in her symposium welcome remarks.

FARA Executive Director Jennifer Farmer introduced the patients and provided insights on their participation in studies and clinical trials.

The USF Health Morsani College of Medicine is one of 10 sites in the international FARA Collaborative Clinical Research Network, all working to discover treatments that can attack FA on different fronts and improve the quality of life for patients.

“We’ve made this a high research priority within the institution,” President Genshaft said. “Over the last 20 years FARA’s international collaborative of researchers has increased the pace in the fight against FA. Today more than 20 drugs are in the treatment pipeline and ongoing studies are working toward the discovery of new therapies… We have every reason to be hopeful, but we do know there is more work to be done.”

Theresa Zesiewicz, MD, professor of neurology and director of the USF Ataxia Research Center, presented promising preliminary results from two clinical trials conducted at USF, among other sites. – Photo by Kent Ross

Theresa Zesiewicz, MD, professor of neurology and director of the USF Ataxia Research Center, updated attendees on the center’s initiatives.

“We started out at USF with one clinical trial eight years ago, and now we have five or six clinical trials and each (investigational) drug works differently,” Dr. Zesiewicz said. “Some drugs work to increase frataxin (the protein depleted in those with FA), some drugs work on inflammation, some work as strong antioxidants. So, there may not be one magic bullet to stop this disease; rather, it may require a cocktail of therapies, a conglomerate of different compounds to help delay or stop the disease process.”

David Lynch, MD, PhD, (center) lead investigator for the FA Natural History Study at Children’s Hospital of Philadelphia, responds to a patient question. He was joined in the discussion of clinical trials by Martin Delatycki, PhD, (far left) of Murdoch Children’s Research Institute, Melbourne, Australia.

Some promising preliminary results for two clinical trials conducted at USF, among other sites, were announced by lead investigator Dr. Zesiewicz. Both studies were done in collaboration with FARA.

• EPI-743 Safety and Effectiveness Study: The Phase 2 open-label extension study, sponsored by Edison Pharmaceuticals, tested the effectiveness of the potent antioxidant EPI 743 primarily on vision, and secondarily, on neurological function in adult patients with FA. After two years of study and a year of data analysis, the researchers found that patients taking EPI-743 from the study’s start demonstrated markedly less disease progression than would be expected in the natural history of the disease. The improvement in neurological function was dose-dependent, and although the last 18 months of the study were open-label, patients and investigators were blinded to the drug dose allocation. Additional studies of EPI-743 are planned in pediatric patients and those with point mutations.

FARA President Ron Bartek thanked everyone in the room, including researchers, pharmaceutical partners and patients and their families, for working together to advance discoveries to “slow, stop and reverse” Friedreich’s ataxia.

• Retrotope RT001 Phase 1/2: The randomized double-blind, placebo-controlled trial evaluated the safety, tolerability and early effectiveness of the stabilized fatty acid RT001 in adult patients with FA. In the small, 28-day study, researchers found that the drug was safe, well tolerated at high doses and rapidly absorbed to target levels, with early signs of effectiveness. Earlier this year, the FDA granted Retrotope orphan drug designation for RT001 in FA.

The scientist and physician panelists at the symposium covered four areas of FA research:

• Basic and Discovery Science: Helene Puccio, PhD; Marek Napierala, PhD; and Jordi Magrane, PhD
• Drug Development and Advancing Treatments: Mark Payne, MD; and Barry Byrne, MD, PhD.
• FA Biomarkers: Kimberly Lee Lin, MD; Angel Martin, PhD student; and Christophe Lenglet, PhD.
• Clinical Trials and Translating Treatments to Improved Care: Martin Delatycki, PhD; and David Lynch, MD, PhD.

The researchers discussed their scholarly work, progress beyond their laboratories and its relevance to advancing treatments. They also emphasized their passion for FA science and personal commitment to patients.

Scientists participating in the Basic and Discovery Science panel discussion were, from left, Jordi Magrane, PhD, of the Brain and Mind Research Institute, Weill Cornell Medical College; Marek Napierala, PhD, of the University of Alabama; and Helene Puccio, PhD, of the Institute of Genetics and Molecular and Cellular Biology, University of Strasbourg.

Moving from treating symptoms to slowing and stopping progression to reversing disease is “not an overnight event,” said David Lynch, MD, PhD, lead investigator for the FARA Natural History Study at Children’s Hospital of Philadelphia. “So, in 15 years we may look back and talk not about the advance but about the 15 advances from each of 15 clinical trials superimposed on top of one another, eventually leading to that four letter word — cure.”

Answering patient questions on drug development and advancing treatments were physician-scientists Barry Byrne, MD, PhD, (left) of the University of Florida College of Medicine; and R. Mark Payne, MD, of Indiana University School of Medicine.

Despite the challenges, the researchers agreed that the steadfast determination and resilience of patients and their families energizes them to keep working toward a cure.

“Everything we do is for the patients, and we are all in this together trying to find a treatment and cure for Friedreich’s ataxia,” said USF’s Dr. Zesiewicz. “That’s the only reason we’re here.”

Participants in the FA BioMarkers panel discussion were, from left, Kimberly Lee Lin, MD, of Children’s Hospital of Philadelphia; Christophe Lenglet, PhD, of the Institute for Translational Neuroscience, University of Minnesota; and Angel Martin, a PhD candidate at Duke University.

Alison Avery, second from right, credits her family — sister Laurel Avery (left) and parents Paul and Suzanne Avery — with “never really letting me believe that Friedreich’s ataxia is going to stop me.”

Dr. Zesiewicz with members of the USF Ataxia Research Center, one of 10 sites in the international FARA Collaborative Clinical Research Network. – Photo by Kent Ross

Photos by Eric Younghans and video by Sandra C. Roa, USF Health Communications and Marketing

The U.S. Food and Drug Administration yesterday designated fast-track status to EPI-743 for the treatment of Friedreich’s ataxia – a move that will help accelerate clinical development of the investigational drug, currently being tested in a multisite, double-blind, placebo-controlled trial led by the University of South Florida.

The phase 2b clinical trial of EPI-743 in adults with Friedreich’s ataxia, sponsored by Edison Pharmaceuticals, Inc., in collaboration with the Friedrich’s Ataxia Research Alliance, has been underway since early 2013 at the USF Health, the Children’s Hospital of Philadelphia and the University of California in Los Angeles.  Neurologist Theresa Zesiewicz, MD, director of the USF Ataxia Research Center, is the lead investigator for the national trial.

Researchers are primarily testing the effectiveness of EPI-743, a potent antioxidant, on vision, in patients with Friedreich’s ataxia, many of whom experience varying degrees of visual changes. Secondarily, the study is evaluating neurological function.

For more on the fast track status of EPI-743, go to: http://www.firstwordpharma.com/node/1195801#axzz2wKgT2a1W

First patient enrolled to evaluate investigational drug’s effectiveness  in rare Friedreich’s ataxia genotype

Mountain View, CA; Downingtown, PA; & Tampa, FL (Nov. 4, 2013) — Edison Pharmaceuticals, the Friedreich’s Ataxia Research Alliance (FARA) and the University of South Florida (USF) today announced the initiation of a phase 2 study entitled, “Phase 2A Clinical Trial of EPI-743 on Visual Function in Friedreich’s Ataxia Patients with Point Mutations.”

Given the rarity of the Friedreich’s ataxia point mutation genotype, the trial is a single-arm, subject-controlled study lasting three months, followed by a three-month extension phase.  Study participants must be between the ages of 18 and 65, possess genetic confirmation of Friedreich’s ataxia point mutation defect, and meet certain disease severity criteria. The primary endpoint of the trial is visual function, with secondary endpoints including neurological and neuromuscular function, and disease-relevant biomarkers.  More information on study specifics is available on ClinicalTrials.gov.

This trial will be conducted at USF Health – a member of the Collaborative Clinical Research Network in Friedreich Ataxia– and is funded by a grant awarded by the Friedreich’s Ataxia Research Alliance. The study sponsor is USF, and the principal investigator is Theresa A. Zesiewicz, MD, FAAN, professor of neurology and director of the USF Ataxia Research Center.

“FARA has been eager to see drug development efforts extend into ultra-rare subgroups of Friedreich’s ataxia, such as those harboring point mutations,” said FARA President Ronald Bartek. “This is the first study dedicated to examining safety and investigational drug response in adults with point mutations in the frataxin gene that represent approximately 2 to 4 percent of the Friedreich’s ataxia patients.”

EPI-743 is currently being evaluated in a phase 2B placebo-controlled Friedreich’s ataxia trial in individuals with the more common triplet repeat expansion defect in frataxin synthesis.

Friedreich’s Ataxia

Friedreich’s ataxia is an autosomal recessive nuclear DNA inherited mitochondrial disease, affecting an estimated 1 in 30,000 individuals in the United States and Europe. Friedreich’s ataxia is caused by a defect in the gene frataxin, which encodes a 210 amino acid protein that participates in iron-sulfur (Fe-S) cluster protein assembly. As the majority of these Fe-S cluster proteins are localized in the respiratory chain in the mitochondria, patients with Friedreich’s ataxia present with “energy failure” symptoms including ataxia, muscle weakness, heart failure, diabetes, and visual, speech, and hearing deficiencies. Friedreich’s ataxia is a highly debilitating and life-shortening disease and is a member of a larger family of diseases called mitochondrial disease that share as a common biochemical mechanism defects in cellular energy metabolism. There are no FDA-approved drugs for Friedreich’s ataxia.

EPI-743

EPI-743 is an orally bioavailable small molecule being developed by Edison Pharmaceuticals for the treatment of Friedreich’s ataxia and other inherited mitochondrial diseases.

Edison Pharmaceuticals

Edison Pharmaceuticals is a biotechnology company dedicated to developing treatments for children and adults with mitochondrial diseases. More information can be found at www.edisonpharma.com.

FARA

The Friedreich’s Ataxia Research Alliance (FARA) is a national, public, 501©(3), non-profit, tax-exempt organization dedicated to curing Friedreich’s ataxia (FA) through research. FARA grants and activities provide support for basic and translational FA research, pharmaceutical/ biotech drug development, clinical trials, and scientific conferences. FARA also serves as a catalyst, between the public and scientific community, to create worldwide exchanges of information that drive medical advances. For more information about FARA, visit them online at www.curefa.org.

USF Health

USF Health is an integral part of the University of South Florida, a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities. USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. For more information, visit www.health.usf.edu.

Natchez Hanson considers one of her proudest accomplishments walking across the stage to receive her college diploma – earning a bachelor’s degree in math education.   Hansen, 24, now a high school math teacher in Polk County, lives daily with the challenges of Friedreich’s ataxia.

Friedreich’s ataxia, a rare debilitating neuromuscular disease, typically strikes between the ages of 5 and 15, causing vision, balance, speech and cardiac problems and progressively robbing a young person of their energy, strength and ability to walk.

While physical therapy helps Hanson work on core strength and balance, there is no approved treatment for Friedreich’s.  That’s why she is so excited to be part of a USF-led national clinical trial of a drug that researchers, clinicians and patents hope will be the first to improve the symptoms of the life-shortening disease.

USF Health neurologist Dr. Theresa Zesiewicz, left, with patient Natchez Hanson, one of the participants in the USF-led national clinical trial for a potential Friedreich’s ataxia drug.

“I don’t want anyone else to feel the way I did (when I was diagnosed) if they don’t have to,” Hanson said. “I just cried because it was scary. A lot of people died being really young, and I was only 17.  I had all these dreams… I just wanted to be normal.”

The double-blind, placebo-controlled trial, sponsored by Edison Pharmaceuticals, Inc., in collaboration with the Friedreich’s Ataxia Research Alliance (FARA), is led by neurologist Dr. Theresa Zesiewicz, director of the USF Ataxia Research Center.

Researchers are primarily testing the effectiveness of the investigational drug EPI 743, a potent antioxidant, on vision, in patients with Friedreich’s ataxia, many of whom experience varying degrees of visual changes. Secondarily, the study will evaluate neurological function.

Sixty patients with a genetically-confirmed Friedreich’s ataxia diagnosis have been enrolled in the study, which involves Children’s Hospital of Philadelphia at the University of Pennsylvania and UCLA in Los Angeles, CA, as well as lead site USF.

When the study was announced at last year’s USF/FARA Scientific Symposium, the news was welcomed with cheers and tears by patients and their families who had come to learn about the latest advances in ataxia research.

The reaction and subsequent overwhelming international interest by prospective trial participants did not surprise Dr. Zesiewicz and others who care for those with Friedreich’s ataxia.

“These are young people – children, teens, young adults – affected by a relentless disease that can cause early death,” said Dr. Zesiewicz, USF Health professor of neurology.  “There is a real sense of urgency to find a first treatment … We’re racing against time here.”

EPI-743 isn’t the only drug in the pipeline for Friedreich’s ataxia and related disorders, but it has shown promise in some early, limited trials —  including a study showing neurological benefit in children with Leigh syndrome, a mitochondrial disease, like Friedreich’s, that attacks energy metabolism.  And, so far at least, the drug appears to be well tolerated.

EPI-743 is an extremely powerful antioxidant — much stronger than the vitamin E you can get at a drugstore, Dr. Zesiewicz said. “The thinking is that this very powerful antioxidant will work on the energy-producing part of the cell, the mitochondria, to improve symptoms.”

While Friedreich’s ataxia is the focus of the USF-led study, Dr. Zesiewicz said, “EPI-743 may have implications for other neurodegenerative disorders like Parkinson’s disease and Alzheimer’s disease.”

USF is one of 10 partners in the FARA Collaborative Clinical Research Network, an international network of centers sharing and resources to advance treatments and clinical research for people with Friedreich’s ataxia.

The USF Ataxia Research Center conducts several studies in addition to the EPI-743 trial, including a clinical study on cardiac dysfunction in Friedreich’s ataxia and another looking for biomarkers to better monitor disease progression.

Edison Pharmaceuticals CEO Dr. Guy Miller, said USF was the logical choice to take the lead role in the latest EPI-743 trial.

“Many centers have silos of excellence in basic science, or clinical research, or translational research, but at USF there is a cross-section of excellence in all three, which is essential for conducting a well-run 2B clinical trial.  ” Dr. Miller said. “You also have a fantastic alignment of physician leaders who are innovative and care deeply about patients.”

L to R: Dr. Stephen Klasko and Dr. Zesiewicz with Dr. Guy Miller, CEO of Edison Pharmaceuticals, at last year’s USF/FARA Scientific Symposium, where Dr. Miller announced the EPI-743 clinical trial for Friedreich’s ataxia. Dr. Miller returned to this year’s symposium, giving an update on drug discovery innovation and progress.

Dr. Clifton Gooch, chair of USF Health Neurology and director of the USF Neuroscience Collaborative, emphasized both the rapid rise of the center and the prospects for EPI-743.

“The USF Ataxia Research Center has become a leading international clinical trials center in just a few short years under Dr. Zesiewicz’s dedicated leadership, and we are excited to now be testing one of the most promising drugs yet tried for the treatment of FA,” he said.

Friedreich’s ataxia is a caused by defects in the gene carrying instructions for a protein called frataxin, which leads to diminished energy production in cells, including those of the nervous system and heart.  While rare – only one in 50,000 people are affected by the inherited disease – one in 100 carry the gene, many without even being aware of it.

“Mom and Dad carry the Friedreich’s ataxia gene, but neither one knows that they carry the gene, so it’s often a big surprise to the parents when the child is diagnosed,” Dr. Zesiewicz said.

For many children the first sign that something is physically wrong are falls. That’s what Hanson remembers.

“When I was growing up, I always walked a little goofy,” she said.  “I would run and fall down, but then I’d just get right back up and start running again.”

As time progressed she had trouble walking in a straight line, and leaned on friends and family for support, eventually graduating to crutches.   After physicians ruled out several other potential causes, including a brain tumor, Hanson was formally diagnosed with Friedreich’s ataxia at age 17.   She started using a walker two years ago.

At first, Hanson said, she was embarrassed by the walker, but now she embraces the greater mobility it provides and uses its storage compartment to help carry school supplies.  “At least no one thinks I’m drunk anymore, so that’s good,” she quips.

Results of the Edison EPI-743 trial are expected later next year.  In the meantime, Hanson continues to move forward, refusing to let a disease stop her. For the third consecutive year, she was among the patients who spoke Sept. 5 at the 5th Annual USF-FARA Scientific Symposium — sharing their stories of living as optimistically as possible with Friedreich’s ataxia.

“You only have one life, and everyone has a burden to bear.  You either laugh about it or you cry about it – and I’m done crying,” she said.  “I’m trying to be as happy as I can be.”

See related story: USF/FARA scientific symposium to share latest advances in ataxia research

Photos by Aimee Blodgett, USF Communications and Marketing

Friedreich’s Ataxia Research Alliance and University of South Florida host Sept. 5^th event

//www.youtube.com/watch?v=NWZxaPjI_wo

Tampa, FL (August 28, 2013) – Leading scientists and clinicians searching for a treatment for Friedreich’s ataxia (FA) and related disorders will gather for the fifth annual scientific symposium “Understanding a Cure,” 6 to 8 p.m., on Thursday, Sept. 5, at the USF Health Center for Advanced Medical Learning and Simulation, or CAMLS, 124 South Franklin Street, Tampa, FL  33602.

The symposium, free and open to the public, is hosted by the Friedreich’s Ataxia Research Alliance (FARA) and the University of South Florida (USF) Ataxia Research Center.  Speakers will share the latest advances in research — from harnessing stem cell technology to investigating the effectiveness of a new medication.

The event routinely draws patients with Friedreich’s ataxia and their families from across the country to share their thoughts and perspectives about energizing the search for a cure.  The event will also be attended by supporters of the FARA Energy Ball, held on Saturday, Sept. 7.

For the second year in a row, the scientific symposium will be broadcast through the FARA Facebook page, with opportunities for visitors to join the conversation long distance.  To watch the presentations in real-time, visit https://www.facebook.com/CureFA/app_196506863720166 on Sept. 5 at 6 p.m. EST.  A Facebook account/membership is not needed to join.

Friedreich’s ataxia is a rare, debilitating neuromuscular disorder. Symptoms, emerges either between ages 5 and 15 or in adulthood and can progress to severe disability and include the following: loss of coordination and muscle weakness that leads to wheelchair use, energy deprivation and fatigue, vision impairment, hearing loss, slurred speech, aggressive scoliosis, diabetes, and life-shortening cardiac disease. There is not yet an approved treatment or a cure.

At last year’s symposium, Guy Miller, MD, PhD, CEO of Edison Pharmaceuticals Inc., announced that USF would lead a multisite study testing the safety and effectiveness of a potent antioxidant, the investigational drug known as EPI-743, for patients with Friedreich’s ataxia. Dr. Miller will return this year to report on the progress of that ongoing Edison-funded clinical trial, led by Theresa Zesiewicz, professor of neurology at USF Health.

Dr. Zesiewicz will join the discussion about the EPI-743 trial and update attendees on several other studies being conducted by the USF Ataxia Research Center.

Symposium speakers will include Mirella Dottori, PhD, principal investigator and senior research fellow at the Centre for Neuroscience Research, University of Melbourne, Australia, who will talk about //www.youtube.com/watch?v=TnLGtN8RVR4

Friedreich’s ataxia treatments with stem cells. Using skin cells from Friedreich’s ataxia patients converted into pluripotent stem cells, Dr. Dottori’s team recently induced these stem cells to generate the specific cell types that degenerate in Friedreich’s ataxia, including heart and nerve cells.

FARA President Ron Bartek and Jennifer Farmer, FARA executive director, will address progress nationwide in the research and management of Friedreich’s ataxia.

Dr. Zesiewicz will moderate a question-and-answer session on patients’ perspectives of living with ataxias, and Clifton Gooch, MD, chair of neurology at USF Health, will provide closing remarks.

USF is one of 10 sites included in FARA’s Collaborative Clinical Research Network, an international network of centers that share data and resources to advance treatments and clinical research for people with Friedreich’s ataxia.

For more information, please visit http://www.curefa.org/energyball/sep5.html or call (813) 974-5909.

– About USF Health –

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities. For more information, visit www.health.usf.edu

       – About The Friedreich’s Ataxia Research Alliance (FARA) –

FARA is a non-profit organization dedicated to curing FA through research. FARA grants and activities provide support for basic and translational FA research, pharmaceutical/biotech drug development, clinical trials, and scientific conferences. For more information, go to www.curefa.org.

Video produced by USF Health Communications