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Milestones in ataxia

Authors


  • Relevant conflict of interest/financial disclosures: Nothing to report.

    Full financial disclosures and author roles may be found in the online version of this article.

  • Thomas Klockgether receives and has received research support from the Deutsche Forschungsgemeinschaft, the Bundesministerium fúr Bildung und Forschung, and the European Union. H. Paulson receives and has received research support from the National Institutes of Health (NIH), the National Ataxia Foundation (NAF), Fauver Family Ataxia Research Fund, the Dystonia Medical Research Foundation, and Shire Human Genetic Therapy.

Abstract

The past 25 years have seen enormous progress in the deciphering of the genetic and molecular basis of ataxias, resulting in improved understanding of their pathogenesis. The most significant milestones during this period were the cloning of the genes associated with the common spinocerebellar ataxias, ataxia telangiectasia, and Friedreich ataxia. To date, the causative mutations of more than 30 spinocerebellar ataxias and 20 recessive ataxias have been identified. In addition, there are numerous acquired ataxias with defined molecular causes, so that the entire number of distinct ataxia disorders exceeds 50 and possibly approaches 100. Despite this enormous heterogeneity, a few recurrent pathophysiological themes stand out. These include protein aggregation, failure of protein homeostasis, perturbations in ion channel function, defects in DNA repair, and mitochondrial dysfunction. The clinical phenotypes of the most common ataxia disorders have been firmly established, and their natural history is being studied in ongoing large observational trials. Effective therapies for ataxias are still lacking. However, novel drug targets are under investigation, and it is expected that there will be an increasing number of therapeutic trials in ataxia. © 2011 Movement Disorder Society

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