Pharmacological therapeutics in Friedreich ataxia: the present state

ABSTRACT

Introduction: Friedreich ataxia (FRDA) is a progressive, inherited, neurodegenerative disease for which there is currently no cure or approved treatment. FRDA is caused by deficits in the production and expression of frataxin, a protein found in the mitochondria that is most likely responsible for regulating iron-sulfur cluster enzymes within the cell. A decrease in frataxin causes dysfunction of adenosine triphosphate synthesis, accumulation of mitochondrial iron, and other events leading to downstream cellular dysfunction.

Areas covered: Therapeutic development for FRDA currently focuses on improving mitochondrial function and finding ways to increase frataxin expression. Additionally, the authors will review potential approaches aimed at iron modulation and genetic modulation. Finally, gene therapy is progressing rapidly and is being explored as a treatment for FRDA.

Expert commentary: The collection of multiple therapeutic approaches provides many possible ways to treat FRDA. Although the mitochondrial approaches are not thought to be curative, as the primary frataxin deficit will remain, they may still produce improvements in quality of life and slowing of progression. Therapies aimed at frataxin restoration are more likely to truly modify the disease, with gene therapy as the best possibility to alter the course of the disease from both a cardiac and neurological perspective.

KEYWORDS:

• Coenzyme Q10
• deferiprone
• Friedreich ataxia
• gene therapy
• idebenone
• interferon gamma
• methylprednisolone
• mitochondrial dysfunction
• TAT-frataxin
• thiamine

Declaration of interest

D Lynch has received grant funding from the Friedreich Ataxis Research Alliance, MDA, Santhera, Penwest, Edison, Viropharma/Shire Pharmaceuticals, has consulted for Retrotrope and Apopharma, and has collaborated with Repligen. J Larkindale is an employee of the Friedreich Ataxia Research Alliance. 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.

Additional information

Funding

This paper was supported by the Friedreich’s Ataxia Research Alliance.