par Pandolfo, Massimo 
Référence Movement disorders, Elsevier Inc., page (649-655)
Publication Publié, 2005
Référence Movement disorders, Elsevier Inc., page (649-655)
Publication Publié, 2005
Partie d'ouvrage collectif
| Résumé : | Friedreich's ataxia (FA) is an autosomal recessive disease characterized by progressive neurological disability, cardiomyopathy, and increased risk of diabetes mellitus. The first symptoms usually appear in childhood, but the age of onset may vary from infancy to adulthood. Atrophy of sensory and cerebellar pathways causes ataxia, dysarthria, fixation instability, deep sensory loss, and loss of tendon reflexes. Corticospinal degeneration leads to muscular weakness and extensor plantar responses. A hypertrophic cardiomyopathy may contribute to disability and cause premature death. Kyphoscoliosis and pes cavus are common. Investigations have unequivocally revealed that frataxin deficiency leads to loss of function of Fe-S center containing enzymes, excessive free radical production in mitochondria and progressive iron accumulation in these organelles. Ongoing biochemical and structural studies are aimed at understanding the specific function of the protein. Additionally, a study has demonstration that frataxin overexpression is not toxic and could be a good therapeutic approach. Gene therapy strategies that would efficiently deliver frataxin expression to cells affected in FA can be envisaged to increase frataxin levels in FA patients. Increases of frataxin levels to 50% of wild type would be sufficient to stop the progression of the disease. Further studies are needed to assess the feasibility of this therapeutic option and optimize conditions for gene delivery. © 2005 Elsevier Inc. All rights reserved. |
