Rapid and complete reversal of sensory ataxia by gene therapy in a novel model of Friedreich ataxia

Françoise Piguet, Charline de Montigny, Nadège Vaucamps, Laurence Reutenauer, Aurélie Eisenmann, Hélène Puccio, Molecular Therapy , Volume 0 , Issue 0 , DOI: 10.1016/j.ymthe.2018.05.006

Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin positive cells which recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, proprioceptive neurons can survive for many weeks without frataxin, although fully dysfunctional. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue the sensory neuropathy associated with frataxin deficiency, thus establishing the preclinical proof of concept for the potential of gene therapy in treating FA neuropathy.

 Rapid and complete reversal of sensory ataxia by gene therapy in a novel model of Friedreich ataxia