New advances in the treatment of Friedreich ataxia: promises and pitfalls

Abstract

Friedreich ataxia (FRDA) is an autosomal recessive, neurodegenerative disease. It affects primarily the nervous system and the heart. Progressive gait and limb ataxia, dysarthria, loss of vibration and proprioceptive sense are characteristic neurological symptoms in FRDA. In approximately 96% of patients FRDA is caused by a triplet guanine-adenine-adenine expansion within the first intron of the FXN gene on chromosome 9q13. Increased numbers of guanine-adenine-adenine repeats are suggested to interfere with FXN transcription via heterochromatin-mediated silencing and result in frataxin deficiency in FRDA. Genetic and biological studies support the role of frataxin as a multifunctional protein in iron-dependent mitochondrial pathways. Multicenter, randomized-controlled Phase III trials in FRDA failed to prove disease modifying properties of candidate substances until to date. Phase II studies attributed idebenone, a synthetic short chain quinine analogue of co-enzyme Q10, some clinical benefit. Recent Phas...