First in HumanTherapeutic Clinical trial reveals early promise for treatment for Friedreich’s ataxia

Friedreich’s ataxia is an inherited, progressive neuromuscular disease caused by partial inactivation of the frataxin gene. In this proof-of-concept study of epigenetic modification, carried out in the NIHR/Wellcome Imperial Clinical Research Facility, Prof Richard Festenstein and colleagues demonstrated that inhibition of histone deacetylase activity by high dose nicotinamide increases Frataxin to the levels found in carriers without symptoms of the condition. This clinical trial was the culmination of more than 10 years basic research, supported by Ataxia UK and the Medical Research Council (MRC), which now provides proof that aberrant gene silencing can be overcome in humans using an ‘epigenetic modifier’, opening the way to a radical approach for other disorders caused by a similar mechanism.