Translational research in ataxia
Prof. Massimo Pandolfo
Brussel, Belgium 
Disclosure : Research support from Repligen.
Consulting fees from Apopharma and Santhera.
Royalties from Athena Diagnostics.
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51 slide(s) – 00:32:09 – English – 2011-09-11
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Translational research in ataxia has come to maturity during the last decade, when progress in basic research, including generation of better animal and cellular models, has met with the development of new clinical assessment tools and biomarkers. These advances involved in particular Friedreich’s ataxia (FRDA) and some dominant spinocerebellar ataxias (SCAs). EU supported consortia have played a key role, first the FP6 Eurosca project, targeting SCAs, currently the FP7 EFACTS project, targeting FRDA.
Better understanding of the pathogenesis of several SCAs, particularly those due to poly-Q expansions, is leading to the identification of potential therapeutic targets. Examples include the discovery of the role of phosphorylation of serine 776 of ataxin-1 in SCA1 and the identification of neurophysiological abnormalities in Purkinje neurons in various SCAs. Concomitantly, new clinical assessment tools as the SARA scale have been developed and important natural history information has been collected.
In the case of FRDA, the discovery of the epigenetic effect of expanded GAA repeats resulted in therapeutic approaches to restore frataxin levels by acting on chromatin-modifying enzymes. Other approaches to upregulate frataxin, as the use of EPO, have also been proposed. Deeper knowledge about frataxin function and the consequences of its deficiency led to therapeutic attempts with antioxidants (idebenone), iron chelators (deferiprone) and stimulants of mitochondrial biogenesis (pioglitazone). These drugs have been or are being tested in controlled trials, made possible by better clinical knowledge and validated assessment tools.
Finally, evidence-based assessments of symptomatic treatments for ataxia and of rehabilitation procedures are being carried out.
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