Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich's ataxia

Amandine Palandri, Elodie Martin, Maria Russi, Michael Rera, Hervé Tricoire, Véronique Monnier, Disease Models & Mechanisms 2018 : dmm.033811 doi: 10.1242/dmm.033811 Published 13 June 2018

In conclusion, this pharmacological screen led to the identification of 11 drugs that significantly reduced heart dilatation of frataxin-depleted hearts. This study may lead in the future to therapeutic applications and improves our knowledge of the mechanisms involved in cardiac dysfunction associated with FA disease. In particular, it suggests that decreased contractility and dilatation of frataxin depleted hearts are, at least in part, a consequence of defective sarcomeric assembly due to microtubule destabilisation. More generally, our data highlight the power of Drosophila models of cardiac diseases for pharmacological approaches. We show here that it is feasible to perform pharmacological screens in vivo on a relatively large scale, under physiological conditions and using relevant functional parameters as readouts. This type of approach could therefore be extended in the future to a wide panel of cardiac diseases.