The number of promising treatments for Friedreich ataxia has increased dramatically over the past 10 years. But before a new discovery is approved as a treatment, it must be thoroughly evaluated by preclinical (cell and animal) studies and then by phase I, II and III clinical trials, each designed to answer a different question about the treatment:

Phase I: The treatment is tested in a small group of people to determine a safe dosage range and identify side effects.

Phase II: The treatment is given to a larger group of people for further evaluation of its safety and to determine if it is effective.

Phase III: The treatment is given to large groups of people to confirm its effectiveness, safety and side effects.


Treatments 3 September

Phase III

ACTIMMUNE ® (Interferon gamma-1b)

The phase II open label study of Interferon gamma in Philadelphia (12 children with Friedreich ataxia) showed significant improvement in FARS scores and a small increase in Frataxin levels, and there were no serious adverse effects ( Based on these encouraging results, Horizon Pharma has initiated a Phase III clinical trial of ACTIMMUNE. (

Phase II


Edison Pharmaceuticals has completed recruitment for a phase II double blind, placebo controlled clinical trial of EPI-743 (a drug with close similarities to EPI-A0001, which aims to improve mitochondrial function) in Friedreich ataxia patients. The primary outcome measure is visual function. Results of the trial are expected in the third quarter of 2015. (


RTA 408 (Nrf2 activator)

Reata Pharmaceuticals has developed a compound, RTA 408, to target activation of the transcription factor Nrf2, a protein that is essential for protecting cells from oxidative stress and has reduced activity in frataxin deficient cells. Recruitment for a phase II clinical trial began recently in the United States and the estimated completion date is mid-2016. (



In an open label pilot study of nicotinamide (vitamin B3), an HDAC inhibitor, Frataxin levels increased in blood samples from participants but the neurological measures did not show significant improvement ( While these results are of interest, further studies of longer duration are needed to determine if nicotinamide is safe and effective as a long-term treatment for Friedreich ataxia. Recruitment for a follow-up study is now underway in London, with an estimated completion date of September 2016. (


ALCAR (Acetyl-L-Carnitine)

Dr. Theresa Zesiewicz (University of South Florida) has initiated an open label study of ALCAR (Acetyl-L-Carnitine), a well-researched nutritional supplement that may be beneficial in cardiovascular disease and neurodegenerative disorders. ALCAR is a more bioavailable form of L-carnitine, a derivative of the amino acid lysine that is made naturally in the body. It functions as an antioxidant and has an important role in glucose metabolism. The 24-month study will examine cardiac and neurological measures in FRDA adults and is open for enrollment. (



Several reports have suggested that erythropoietin (EPO) can increase frataxin levels. A phase II clinical trial is being conducted by Dr. Francesco Saccà in Italy to test the effect of EPO on exercise capacity in FRDA patients. The treatment phase has been completed and results should be reported by the third quarter of 2015. (



Resveratrol is found in the skin of red grapes and has been investigated as a compound that could improve mitochondrial function. Pre-clinical laboratory studies in Friedreich ataxia cell and mouse models indicated that resveratrol also increases Frataxin levels. Thus, Professor Martin Delatycki and his colleagues carried out an open label pilot study in Friedreich ataxia patients to evaluate the safety, tolerability and efficacy of two different doses of resveratrol ( While Frataxin levels did not change at either dose, participants taking the higher dose showed improvement in FARS and speech measures, but they also had gastrointestinal side-effects. A placebo-controlled clinical trial is now being considered. (

Phase I


ViroPharma (acquired by Shire in November 2013) initiated a phase I double blind, placebo controlled clinical trial of SHP622 / OX-1 (indole-3-propionic acid, a naturally occurring compound that has potent anti-oxidant properties) in adults with Friedreich ataxia. The results of this study should be available within the next few months. (


Incretin analogs

Incretins are gut hormones that stimulate insulin secretion to control blood sugar levels. Research on diabetes in Friedreich ataxia led Drs. Miriam Cnop, Mariana Igoillo-Esteve and Massimo Pandolfo to the discovery that incretin analogs induce frataxin expression in pancreatic b-cells and iPSC-derived neurons from Friedreich ataxia patients ( Based on these findings, this team recently launched a small, short-term pilot clinical trial of incretin analogs in Friedreich ataxia patients in Belgium.



Polyunsaturated fatty acids (PUFAs) are needed by cells in the nervous system, but they are susceptible to oxidative damage, which may lead to mitochondrial dysfunction, particularly in individuals with neurological diseases. Retrotope evaluated chemical substitutes in which the hydrogen molecules in PUFAs are replaced with deuterium (a stable isotope of hydrogen) and found that dPUFAs had a protective effect in Friedreich ataxia cell models ( Recruitment for a 28-day clinical trial to evaluate RT001, a dPUFA developed by Retrotope, was announced in August 2015. The trial is taking place at the University of South Florida and UCLA.

Pre-Clinical Studies

HDAC inhibitors

Repligen’s clinical trial in Italy to evaluate the safety and dosage of the HDAC inhibitor, RG2833, has been completed. The treatment was well tolerated and frataxin expression was increased in blood samples from participants, which is encouraging ( However, it has been shown that metabolites formed when RG2833 is broken down in the body can be harmful over the long term. Thus, BioMarin, which acquired the HDAC inhibitor program from Repligen in January 2014, is now developing a follow-on compound with improved metabolic stability and better access to the central nervous system.


Gene Therapy

The Friedreich ataxia MCK mouse model develops a severe cardiac phenotype. Dr. Hélène Puccio’s group demonstrated the prevention and reversal of cardiomyopathy using AAV gene therapy ( Following these exciting results, a new company, AAVLife, has been founded to move the development of gene therapy for FRDA cardiomyopathy forward as rapidly as possible. In April 2014 REGENX Biosciences, a leader in AAV gene therapy, announced that the company has entered into an agreement with AAVLife to develop and commercialize products to treat FRDA using a proprietary vector technology that includes novel AAV vectors. REGENX announced a similar agreement with the new gene therapy company, Voyager Therapeutics, in June 2014, and in February 2015 Voyager Therapeutics and Genzyme entered a major strategic collaboration, which is focused on developing and commercializing novel AAV gene therapies for patients with CNS diseases, including FRDA. Additionally, engineering innovative DNA-based therapeutics for FRDA is the lead program of Agilis Biotherapeutics, which has an exclusive collaboration agreement with Intrexon Corporation to provide promising new treatments for FRDA.


Frataxin replacement

Using a cell-penetrant peptide (TAT) to deliver human Frataxin protein to mitochondria in Friedreich ataxia cell and mouse models, Dr. Mark Payne reversed the disease phenotype, suggesting the potential of protein replacement therapy ( Bioblast Pharma is pursuing a similar frataxin replacement approach, which they are testing in cell and animal models.


RNA-based approach

RaNA Therapeutics is focusing on identifying non-coding RNAs (ncRNAs) that may contribute to silencing the frataxin gene in Friedreich ataxia patients. Research by this company has shown that degrading specific ncRNAs results in increased expression of the frataxin gene. Thus, this may be a promising therapeutic approach.


Nrf2 activators

Dr. Gino Cortopassi (UC Davis and one of the founders of Ixchel Pharma) screened a library of approved drugs and identified several compounds that activate Nrf2. Together with Dr. Susan Perlman (UCLA), Dr. Cortopassi is doing further laboratory testing of these compounds, including dyclonine, a topical anesthetic, and dimethylfumarate, which has been approved for multiple sclerosis (