Institut National De La Sante Et De La Recherche Medicale

Assistance Publique - Hopitaux De Paris (aphp)

Fondation Imagine

Anne Agnès Rotig

Arnold Munnich

Floriane Petit

Friedreich ataxia (FRDA) is caused by a GAA repeat expansion in FXN gene that encodes a mitochondrial protein, frataxin, involved in iron sulfur complex (ISC) assembly. Frataxin deficiency results in abnormal ISC containing proteins, namely respiratory chain complex I-III and aconitases and accumulation of iron in brain and heart of patients. Here, the inventors show that FRDA fibroblasts are unable to limit iron uptake inducing a massive cytosolic iron accumulation and to a lesser extent in mitochondria. The inventors also observed increased transferrin receptor (TfR1) steady state levels and membrane TfR1 accumulation that they ascribed to impaired post-translational modification by palmitoylation as well as delayed transferrin recycling. Finally, the inventors showed that artesunate, dichloroacetate and Coenzyme-A improved TfR1 palmitoylation and thus represent candidate molecules for the treatment of patients with Friedreich ataxia. Thus the present invention relates to methods of treating Friedreich ataxia (FRDA) as well as to methods of predicting whether a patient suffering from FRDA will achieve a therapeutic response.

Growing community of inventors

Paris, France

Anne Agnès Rotig