USF Health to lead new Friedreich’s ataxia study [VIDEO]
USF Health will be the lead site for a new study testing the safety and effectiveness of a potent antioxidant for patients with Friedreich’s ataxia (FA), a life-shortening, degenerative neuromuscular disorder.
The news was greeted with enthusiasm and rounds of applause when announced Thursday evening at the 4th annual scientific symposium “Understanding a Cure,” hosted by the Friedreich’s Ataxia Research Alliance (FARA) and the USF Ataxia Research Center (ARC).
Logistics are still being finalized for the double-blind, placebo-controlled trial sponsored by Edison Pharmaceuticals Inc. The study will primarily measure the effect of Edison’s investigative drug, known as EPI 743, on vision, including contrast and acuity, in FA patients, many of whom experience varying degrees of visual changes. Researchers plan secondarily to evaluate neurologic function using the Functional Assessment Rating Scale.
Intended to begin by winter 2012, the USF-led study is not currently recruiting participants, but patients with a genetically-confirmed FA diagnosis can register on the FARA Patient Registry, which will connect eligible patients with researchers conducting the trial once recruitment begins.
For the first time the symposium was live streamed through the FARA Facebook page. Viewers across the world visited the stream (more than 1,400 views were recorded), from nearly every continent and as far away as Australia, as well as from coast to coast in the United States. The live event was attended by more than 200 scientists, clinicians, patients and their family members at the USF Health Center for Advanced Medical Learning and Simulations (CAMLS) in downtown Tampa.
Friedreich’s ataxia, marked by progressive loss of balance, coordination and muscle strength, can also impair speech, vision, hearing and lead to diabetes and potentially life-threatening cardiac disease. There is no cure yet.
Dr. Theresa Zesiewicz, professor of neurology and director of the USF ARC, will be principal investigator for the newly announced multi-site EPI-743 study. She will work with co-investigators at two other sites in FARA’s Collaborative Clinical Research Network — Dr. David Lynch at the Children’s Hospital of Philadelphia, University of Pennsylvania, and Dr. Susan Perlman at UCLA in Los Angeles, CA.
“EPI-743 holds great promise as a treatment for FA, which is potentially great news for patients and families,” said Dr. Zesiewicz said. “We’re honored to serve as the lead site, and excited about the opportunity to help advance this leading drug candidate along the treatment pipeline.”
“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 to conduct a well-run 2B clinical trial,” said Dr. Guy Miller, chairman and CEO of Edison Pharmaceuticals, who spoke at the symposium. “You also have a fantastic alignment of physician leaders who are innovative and care deeply about patients.”
Edison focuses on developing drugs to treat inherited mitochondrial diseases that share a common feature – defects in how the body makes and regulates energy metabolism. The loss of function of the protein frataxin in Friedreich’s patients has been associated with the impaired ability of mitochondria in nerve cells to make energy.
Dr. Miller presented encouraging preclinical and preliminary clinical studies for EPI-743, a compound designed to improve mitochondrial function, which represents the most advanced drug candidate in Edison’s portfolio. In the laboratory, EPI-743 – a broader, more potent derivative of the antioxidant CoQ10 — successfully rescued human muscle cells under oxidative stress and returned them to a normal state.
One recent clinical study demonstrated that EPI-743 reversed the progression of mitochondrial disease in children with Leigh’s syndrome, benefitting gross motor function and quality of life among other measures. “Every single patient treated with EPI-743 improved,” Dr. Miller said.
Next, Miller said “we need to see if we get meaningful therapeutic improvements in the upcoming trial with FA patients.”
Other leading researchers featured at the symposium were Dr. Helene Puccio, research director of INSERM, Department of Translational Medicine and Neurogenetics, Institute of Genetics and Molecular Biology; and Mark Payne, a pediatric cardiologist who directs medical and molecular genetics at Indiana University School of Medicine’s Wells Center for Pediatric Research.
Dr. Puccio’s laboratory is renowned for developing mouse models to help understand the pathophysiology of FA and to test potential new treatments, including gene therapy approaches.
Over the last two years, her team has worked out a way to insert human frataxin DNA into the cells of mice using an adeno-associated virus as the delivery vehicle. The “infected” cells then begin expressing the frataxin gene and making the protein severely deficient in FA patients.
Using mice genetically engineered to exhibit the symptoms of heart muscle deterioration (cardiomyopathy) associated with FA, Dr. Puccio showed that gene replacement reversed heart damage in mice that would have died without treatment. In fact, when they looked at cardiac and mitochondrial function, the researchers found no difference between the FA mice treated with the virus-delivered frataxin gene and normal, untreated mice.
“This is very exciting,” Dr. Puccio said. “We had complete rescue of both pre and post-symptomatic mice… It shows we have a wide therapeutic window in mice, and we hope the results can be translated into humans.”
Dr. Payne shared his expertise on heart disease caused by mitochondrial defects, noting that heart failure is a major cause of death for patients with Friedreich’s ataxia. His laboratory has produced evidence that replacing missing frataxin protein in a mouse model for FA helped prevent heart muscle cell death and increased lifespan by 50 percent.
All patients with Friedreich’s ataxia should get yearly cardiac evaluations, Dr. Payne recommended.
The USF ARC will also be a site for an upcoming pilot study examining whether the amino acid L-carnitine can improve cardiovascular outcomes in patients with FA.
FARA President Ron Bartek and Executive Director Jennifer Farmer gave an overview of the progress in FA research at the beginning of the program.
Since FARA was established in 1998, founding member Bartek said, the association’s grant awards have risen from $100,000 (1999) to an estimated $3 million this year, scientific publications have doubled, and drugs in the clinical trial pipeline have gone from zero to 10.
“By scientific standards, the research on this disease is moving at lightning speed,” Bartek said. “Together we will beat and cure Friedreich’s ataxia.”
Following the scientific presentations, a patient panel discussion moderated by Dr. Zesiewicz drove home the importance of the research. Kyle Bryant, Jack DeWitt, Natchez Hanson, Laura Beth Jacquin, and Stephanie Magness answered questions about the challenges of living with Friedreich’s ataxia, their accomplishments and hopes for the future.
Hanson, diagnosed with FA in 2006, recently graduated from the University of Central Florida and works as a high school math teacher. “I walked at my college graduation using my walker, and hands down it was the proudest moment of my life,” she said.
At one point, DeWitt, the youngest panelist at age 12, turned the tables on the scientists in the audience by asking “What does a cure mean to you?”
Several researchers emphasized the importance of improving patients’ quality of life by easing symptoms while striving to find treatments and working toward a cure that reverses FA.
“The real cure will be when I as the dean of a medical school can finally talk about Friedreich’s ataxia as a historical disease,” said Dr. Stephen Klasko, CEO of USF Health and dean of the Morsani College of Medicine.
In closing remarks, Dr. Clifton Gooch, chairman of neurology at USF, acknowledged the passion and determination of patients and their families who work tirelessly with FARA and academic and industry partners to advance the research that will lead to a cure.
“You brought your hands, your hearts, your minds and the fruits of your labor, laid them all on the table and said ‘we’re going to do our best to change our fates,’” Dr. Gooch said. “And tremendous progress has been made… I’m very encouraged about what I’ve heard tonight. I’m cautiously optimistic that we’re on the verge of something great happening in FA on several fronts.”
- Story by Anne DeLotto Baier, and photos by Eric Younghans, USF Health Communications