Drug screening on a new Drosophila cardiac model of Friedreich Ataxia. Veronique Monnier, Hervé Tricoire. BFA Unit, University Paris Diderot, 75205 Paris Cedex 13, France.

   Friedreich Ataxia (FA), the most common hereditary ataxia, is characterised by progressive degeneration of the central and peripheral nervous system, hypertrophic cardiomyopathy and increased incidence of diabetes. FA is caused by reduced levels of frataxin, a highly conserved mitochondrial protein. Drosophila appears as an adequate animal model to study pathogenic mechanisms involved in FA and to test functionally pharmacological compounds. Several groups have previously developed Drosophila models of FA, in which dfh (the ortholog of Fxn) is downregulated by RNAi in various tissues, including the PNS and glial cells. We have developed a new Drosophila cardiac model of FA by targeting dfh-RNAi in cardiomyocytes with a specific RU486 inducible driver. In vivo real time imaging of Drosophila heart, using an innovative technology that we have recently developed, revealed profound impairments in heart function in these animals, including a strong increase in end-systolic and end-diastolic diameters and a decrease in Fractional Shortening. We used this new Drosophila model for drug screening and identified one compound highly efficient to prevent heart dysfunctions induced by dfh deficiency. This validates the use of this FA model to identify new potential therapeutic compounds that should be subsequently tested on other models of the disease.