“Tremendous progress” in race against Friedreich’s ataxia highlighted at USF-FARA scientific symposium [VIDEO]
“What a difference a year makes” was a theme of this year’s Friedrich’s Ataxia Scientific Symposium hosted by USF and the Friedreich’s Ataxia Research Alliance (FARA).
Researchers, clinicians, patients and their families gathered Sept. 4 at the USF Health Center for Advanced Medical Learning and Simulation for the sixth annual symposium, which was also live streamed over Facebook to an international audience.
Along with research updates from leading scientists who have contributed to breakthroughs in the field of Friedreich’s ataxia (FA), the symposium focused on the inspiring stories of patients living with the rare, debilitating neuromuscular disorder.
“I moved to college in August and that was terrifying — but I love it now,” said Emily Young, 18, a freshman at the University of Illinois, when asked what differences she has experienced in 2014.
Young, diagnosed at age 12, has competed as one of the top cyclists in Ride Ataxia Chicago for the past three years.
“It’s great just to be in the starting line getting ready to go,” she said. “I wake up every morning determined not to let this disease define who I am… It’s important to stay motivated and keep fighting. We will find a cure.”
People with Friedreich’s ataxia harbor genetic mutations that limit the production of frataxin, a protein important to the function of the energy-producing factories, or mitochondria, of the cell. This leads to a variety of symptoms, including neurodegeneration that can cause loss of coordination and muscle weakness, energy deprivation and fatigue, vision impairment, slurred speech, aggressive scoliosis, diabetes, and life-shortening cardiac disease. There is not yet an approved treatment or a cure.
Over the last 20 years, an international collaborative network of researchers coordinated by FARA has increased the pace in the fight against Friedreich’s ataxia. Today, more than 20 drugs are in the treatment pipeline, both in various stages of clinical trials and in pre-clinical development. Ongoing studies in cell and animal models also seek to discover potential new therapies for testing. The studies cover a range of therapeutic targets, including finding ways to boost frataxin production, improve mitochondrial function, or gene therapy approaches, to name a few.
“Our goal is to keep the pipeline filled until we get a treatment that works,” said Jennifer Farmer, executive director of FARA. “We know it will likely be a cocktail approach, not a single drug. We need to attack FA from multiple fronts.”
The USF Ataxia Research Center is a major contender in the race to find the first treatment for Friedreich’s ataxia. USF neurologist Theresa Zesiewicz, MD, center director, gave an overview of the center’s clinical and basic science research.
These include an Edison Pharmaceuticals-sponsored, USF-led multisite trial testing the effectiveness of EPI-743, a potent antioxidant, on vision and neurological function in FA patients. The one-year study has been extended for another year, and this spring the U.S. Food and Drug Administration granted fast-track status to EPI-743 – a move that can help accelerate clinical development of the investigational drug,
Another ongoing study at USF is assessing the role of acetyl-L-carnitine on cardiovascular outcomes in patients with FA, who are at risk for diseases of the heart muscle. The USF Ataxia Research Center collaborated with the USF School of Physical Therapy & Rehabilitation Sciences (Dr. Seok Hun Kim and Jeannie Stephenson) on a recently completed study testing biomarkers to more precisely measure the progression of FA.
The symposium guest speakers were:
– Massimo Pandolfo, MD, a neurologist and researcher at Université Libre de Bruxelles at the Hôspital Erasme, and principal investigator of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS). The FA gene was identified in 1996 by an international collaboration led by Dr. Pandolfo, who has since contributed to understanding the FA disease process and its clinical characterization, advancing drug development, conducting research trials and providing clinical care to patients.
– Sanjay Bidichandani, PhD, head of the Section of Genetics at the University of Oklahoma Department of Genetics, was responsible for the discovery of the G130V mutation in FA, typically manifesting a milder form of the disease. He spoke about his research in the field of epigenetics – the study of traits that surround the frataxin gene or control its expression.
– Joel Gottesfeld, PhD, professor in the Department of Molecular Biology, The Scripps Research Institute, LaJolla, CA, focuses on drug discovery, which led to the identification of small molecules known as histone deacetylase (HDAC) inhibitors that reverse frataxin gene silencing. He spoke about a study he co-authored last month in the Annals of Neurology demonstrating that HDAC inhibitors increased frataxin gene expression and protein in the blood cells of patients with Friedreich’s ataxia. Dr. Gottesfeld’s laboratory is working with the biopharmaceutical company Biomarin to advance these molecules as a potential treatment for FA.
– Héléne Puccio, PhD, is research director at the Insititute de Santé et de la Recherche Médicale (INSERM) and team leader at the Institute of Genetics and Molecular and Cellular Biology, University of Strasbourg, France. Her laboratory works to unravel the causes and mechanisms of FA and to develop new cell and animal models. She shared her findings, published this year in Nature Medicine, showing that frataxin gene therapy could correct mitochondrial metabolism and reverse heart damage in mice lacking frataxin in the heart. The research raises the possibility of a gene therapy treatment for FA.
The talks by researchers and FARA leaders were balanced by the dynamic patient panels moderated by Clifton Gooch, MD, chair of the Department of Neurology at USF Health, and Dr. Pandolfo.
Dr. Pandolfo, who earlier emphasized the importance of rigorous science in ensuring that laboratory findings are translated into safe and effective therapies, asked patients Kyle Bryant, 32, and Natchez Hanson, 25, about their experiences participating in clinical trials. Both enrolled in the EPI-743 trial.
Bryant, diagnosed at age 17, is an athlete who competes in adaptive sports and the founder and director of Ride Ataxia, which has raised more than $2 million through cycling events to benefit FARA. Joining the clinical trial process is his way of advancing research that may lead to a first treatment and, hopefully, a cure, Bryant said.
“I’ve gotten to know all the scientists working with FARA, and there is a tremendous amount of respect and trust in the patient community for what you are doing,” he said. “Maybe I won’t see direct benefit for myself from one trial, but it’s the collection of knowledge and collaboration from all the trials that will get us to the next level… It’s not a Hail Mary pass; it’s more like the constant kicking of a door until it falls.”
Hanson, a high school math teacher in Polk County, has enrolled in three FA clinical trials at USF since 2007. “I see you (scientists and clinicians) as the generals, and we’re the soldiers on the battlefield,” she said. “Somebody has to do it, and when that cure does come I really want to be the first in line to know.”
In his concluding remarks, USF Health’s Dr. Gooch reminded the audience of the great strides over the last decade to advance the understanding of Friedreich’s ataxia and develop potential treatments. He pointed to growing interest by pharmaceutical companies to be involved in drug development for Friedreich’s ataxia, which is relatively new and encouraging within rare diseases. He recognized the courage and dedication of patients and their families that continues to inspire the FA community.
“The race has started and we’re at the head of the pack,” Dr. Gooch said of the work being done to find a first treatment for Friedreich’s ataxia.
“The important thing is to make life better for those in the race and improve the lot of humanity, not just now, but for future generations … Tremendous progress is being made. We have a chance to beat FA into the ground and hopefully someday leave it in the dust.”
The FARA Energy Ball on Sept. 6, one of most successful philanthropic events in Tampa, attracted almost 900 attendees and raised nearly $2 million to benefit FARA, and Friedriech’s ataxia research internationally, including at the USF Ataxia Research Center.
Photos by Eric Younghans, USF Health Communications