The major aims of this project are:
1) to evaluate the functional role of sacsin at the synaptic level, in particular its involvement in the control of calcium fluxes in Purkinje neurons at the postsynaptic space;
2) to strengthen the evidence of efficacy of an off-label drug regulating calcium homeostasis in ARSACS, by conducting a preclinical trial at post- symptomatic stage in Sacs-/- mice with a chronic treatment;
3) to dissect the mechanism by which this drug rescues ataxia and Purkinje cell degeneration in Sacs-/- mice, by evaluating effects on deregulated calcium homeostasis, NF bundling or faulty mitochondrial transport, integrated with multi-omics approaches.
Duration: One year
Funding : $100,000
Dr. Francesca Maltecca , Ospedale San Raffaele, Milan Italy.