Autosomal recessive spastic-ataxia of Charlevoix-Saguenay (ARSACS) is a multisystem hereditary ataxia (HA) associated with mutations in SACS, encoding sacsin, a protein whose function is only in part understood. Mutations in SACS impair chaperone-mediated protein-folding activity and mitochondrial (mt) dynamics in Sacs knock-out (KO) mice and human ARSACS cells. Our challenge is to find tools capable to reverse sacsin defects in mice and to identify biomarkers of efficacy in clinical trials. We will use a dual approach: we will analyze mt functionality in Purkinje cells (PCs) needed to fine tuning new treatment opportunities in Sacs KO mice and will seek for prognostic/predictive biomarkers in patients in order to design new intervention strategies aimed at overcoming brain alterations. To cope with brain alterations in ARSACS and in similar neurological conditions with altered mt functionality, we will also test new nanovectors to easy drug delivery in mutant cells.
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Insight into new therapeutic preclinical strategies in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay type