Chapter

Inherited Neuromuscular Diseases

Volume 652 of the series Advances in Experimental Medicine and Biology pp 247-261

Date:

Friedreich Ataxia: An Update on Animal Models, Frataxin Function and Therapies

  • Pilar González-CaboAffiliated withLaboratory of Genetics and Molecular Medicine, Instituto de Biomedicina de Valencia, CSIC, C/Jaume Roig 11 Email author 
  • , José Vicente LlorensAffiliated withDepartament Genètica, Facultat de Biologia, Universitat de València
  • , Francesc PalauAffiliated withLaboratory of Genetics and Molecular Medicine, Instituto de Biomedicina de Valencia, CSIC, C/Jaume Roig 11
  • , Maria Dolores MoltóAffiliated withDepartament Genètica, Facultat de Biologia, Universitat de València

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Abstract

Friedreich ataxia (FRDA) is an autosomal recessive progressively debilitating degenerative disease that principally affects the nervous system and the heart. Although FRDA is considered a rare disease, is the most common inherited ataxia. It is caused by loss-of-function mutations in the FXN gene, mainly an expanded GAA triplet repeat in the intron 1. The genetic defect results in the reduction of frataxin levels, a protein targeted to the mitochondria. Frataxin deficiency leads to mitochondrial dysfunction, oxidative damage and iron accumulation. Studies of the yeast and animal models of the disease have led to propose several different roles for frataxin. Animal models have also been important for dissecting the steps of pathogenesis in FRDA and they are essential for the development of effective therapies. Currently, antioxidant and iron chelation therapies are under evaluation in clinical trials. Gene reactivation, gene therapy and protein replacement strategies for FRDA are promising approaches.

This review focuses on the current models developed for FRDA, the different roles proposed for frataxin and the progress of potential treatment strategies for the disease.

Keywords

Friedreich ataxia Frataxin Mitochondria Iron-sulfur clusters Oxidative stress Oxidative phosphorylation Antioxidant therapy Iron chelators Recombinant human erythropoietin Histone deacetylase inhibitors