New developments in pharmacotherapy for Friedreich ataxia

ABSTRACT

Introduction: Friedreich ataxia (FRDA), a rare disease caused by the deficiency of the mitochondrial matrix protein frataxin, affects roughly 1 in 50,000 individuals worldwide. Current and emerging therapies focus on reversing the deleterious effects of such deficiency including mitochondrial augmentation and increasing frataxin levels, providing the possibility of treatment options for this physiologically complex, multisystem disorder.

Areas covered: In this review article, the authors discuss the current and prior in vivo and in vitro research studies related to the treatment of FRDA, with a particular interest in future implications of each therapy.

Expert opinion: Since the discovery of FXN in 1996, multiple clinical trials have occurred or are currently occurring; at a rapid pace for a rare disease. These trials have been directed at the augmentation of mitochondrial function and/or alleviation of symptoms and are not regarded as potential cures in FRDA. Either a combination of therapies or a drug that replaces or increases the pathologically low levels of frataxin better represent potential cures in FRDA.

KEYWORDS:

• Friedreich ataxia
• idebenone
• coenzyme Q10
• EPI-743
• tat-frataxin
• Nrf2 activators
• interferon gamma
• HDAC inhibitors

Article Highlights

• No treatment or effective therapy for FRDA currently exists; however, clinical trials for multiple drugs are underway.

• Classic grouping of FRDA therapies consists of those that augment mitochondrial function and those that increase frataxin levels; however, gene therapy and drugs that may ameliorate symptoms of FRDA are expanding.

• Therapies tested related to mitochondrial functioning include: Idebenone, coenzyme Q10, EPI-743, VP-20,629, Deferiprone, Dimethyl Fumarate, Omaveloxolone, and deuterated fatty acids.

• Therapies tested or in testing to increase frataxin include: EPO, tat-frataxin, interferon gamma, HDAC inhibition, and nicotinamide.

• Gene therapy: murine model studies have shown promise in their prevention and reversal of both cardiomyopathy and sensory ataxia in FRDA. Some challenges in translating these results in human subjects have been resolved, but other hurdles remain.

This box summarizes the key points contained in the article.

Declaration of interest

D Lynch is the recipient of grants from Bioelectron, Reata Pharmaceuticals and Takeda Pharmaceutical Co Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.