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The Friedreich’s Ataxia Scientific Symposium: Understanding a Cure recently marked its 9th year of bringing dedicated scientists, clinicians, and industry partners with patients and their families to USF – all whom share a commitment to finding effective treatments and a cure for Friedreich’s ataxia and related disorders.  The Tampa Bay region is considered an epicenter for raising funds to support  research for Friedreich’s ataxia, or FA.  This year’s 10th Friedreich’s Ataxia Research Alliance (FARA) Energy Ball, held Saturday, Sept. 29,  following the symposium and the association’s international FA biomarkers meeting, raised a total of $2.5 million to help bridge the gap between discoveries and treatment.

Hosted by FARA and the USF Ataxia Research Center, the scientific symposium drew an audience of 700 — both live at the USF Health Center for Advanced Medical Learning and Simulation (CAMLS) and viewing the event in real-time through YouTube.

From left: Paul Avery, Dr. Theresa Zesiewicz, Dr. Charles J. Lockwood, Dr. Clifton Gooch, Jennifer Farmer, and Ron Bartek

FA is a rare inherited neuromuscular disease, typically diagnosed in children and adolescents, that progressively robs patients of their ability to walk, speak and function and can ultimately lead to early death. Currently, no drugs are approved for the treatment of FA.

Symposium participants discussed the latest FA translational research progress, as well as heard individual patient perspectives and from scientific and industry partners working with academia to move promising therapies into the clinical trial pipeline.  Researchers are attacking the devastating disease using multiple approaches, including working to improve mitochondrial function and inhibit inflammation, to replace the protein (frataxin) deficient in individuals with FA, and to combine gene correction with hematopoietic stem cell therapy. They also look for targeted biomarkers to help clinicians better assess disease progression and the response of individual patients to investigational FA drugs.

USF Health is one of 11 sites in Friedreich’s Ataxia Collaborative Clinical Research Network, an international network of clinical research centers working together to advance treatments and clinical care for those living with FA.  The USF Ataxia Research Center participates in the FA patient registry, the only worldwide registry containing demographic and clinical information on more than 2,000 patients with Friedreich’s ataxia.

Here’s a sampling of what some symposium speakers had to say:

Charles J. Lockwood, MD, senior vice president of USF Health and dean, USF Health Morsani College of Medicine

“Since 2008, this symposium continues to be a major annual event broadcast around the world… We will never stop looking for answers. We will never stop looking for a cure.”

Dr. Zesiewicz, center, with her USF Ataxia Research Center team

Theresa Zesiewicz, MD, professor of neurology and director, USF Ataxia Research Center

“At USF we have several active trials for FA, and we are close to finding a treatment to arrest disease progression and help alleviate some of the symptoms of FA. We are working towards offering even more clinical research in the future.”

From left, the Patient Panel, moderated by FARA Communications Director Felicia DeRosa, included: Laurel Avery of Florida, Sam Hill of Maryland, Annie Hamilton of New York, and Allison Dana of South Carolina.

Patient Panel:  Living with FA and Research Participation

Laurel Avery, 23, Tampa, FL, currently working on her master’s degree in entrepreneurship

“When I first started college, people automatically assumed that I need help with everything.  That’s a misconception, because the FA community is very adaptable and everyone works very hard to be resilient and strong.”

Sam Hill, 14, Annapolis, MD

“I’m proud that I’m able to keep up at school, even though I get tired easily.  I like math and science.”

Advocacy Organization Panel

Sanjay Bidichandani, PhD, FARA scientific director and head of genetics at the University of Oklahoma College of Medicine Department of Pediatrics

“From the beginning of when the FA gene was found until today, all the discoveries are now nodes or targets for therapies being developed.”

Advocacy Organization Panel participants included, from left: Sanjay Bidichandani, PhD, FARA scientific director; FARA President Ron Bartek; and Pat Ritschel, FARA board director

Ron Bartek, FARA president and co-founder

“We realized from the get-go that to develop a treatment and cure for this disease we’d need to build relationships with patients and their families, with academic investigators, with government partners at the NIH, FDA and Congress, and with industry partners.  With our encouragement, all of those stakeholders are now members of the family… Collaboration is FARA’s middle name.”

Pat Ritschel, FARA Board director

“By spending our effort to remove roadblocks, we attract more companies willing to work in this space of FA research… because the way forward is clear and they can see a path to the clinic and (drug) approval.”

The Scientific Panel included, sitting from left: Carole Ben-Maiman, MD, CEO of Chondrial Therapeutics; Stephanie Cherqui, PhD, associate professor at UC San Diego; Hao Wang, PhD, senior scientific director at Clinical Neuroscience-CNS TAU, Takeda Pharmaceuticals; and Kara Eichelkraut, senior manager of patient advocacy for Reata Pharmaceuticals.

Scientific Panel – FA Treatment Approaches

Jennifer Farmer, FARA executive director

“We have lots of different treatment approaches in various stages of development.  This is very important, because we know that there is no disease fully treated with just one drug or one therapy.”

Hao Wang, PhD, senior scientific director of Clinical Neuroscience-CNS TAU, Takeda Pharmaceuticals

“The patients have educated us about their diagnosis and journey, and what kind of treatments they need. They have a great sense of humor despite the difficulties they are experiencing… The feedback we received from them has helped with study design.”

(Takeda’s investigational drug candidate TAK-831 is in a phase 2 clinical study to evaluate the enzyme inhibitor’s effectiveness on upper extremity motor function and manual dexterity.)

Kara Eichelkraut, senior manager of patient advocacy, Reata Pharmaceuticals

“Anything and everything anyone in this room does to contribute to FA research makes a difference.  If it’s participation in a clinical trial that’s great, but if you cannot do that there are other things you can do, like providing a cheek swab or giving a vial of blood.”

(Reata received orphan drug designation for omaveloxolone for investigational treatment of FA by the FDA and EMA. FARA is enrolling 100 patients in a phase 2, part 2 clinical trial.)

Closing Comments

Clifton Gooch, MD, chair of neurology, USF Health Morsani College of Medicine, thanked participants for their courage and inspiration

“Twenty years after the founding of FARA we have over a dozen clinical trials focused on getting at the very heart of this disease in the genes themselves, using techniques of genetic engineering and modulation, therapies to support the mitochondria, and others… There is great reason for hope.

“Once we find the genetic therapy that treats this disease we will have the tools to prevent it in those who have the aberrant gene, to fix the gene so that they never develop the disease… That’s the world we’re working towards. We want to make FA a footnote in the medical literature, like smallpox.”

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-Videos by Torie M. Doll, and photos by Eric Younghans, USF Health Communications and Marketing

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