ARSACS is characterised by the lack of sacsin expression and the formation of intermediate filaments bundles in neurons and fibroblasts derived from skin biopsies. Our strategy over the last years has been aimed at developing a replacement therapy, by peptide and/or gene vectors and, because of the chaperone function of sacsin, to investigate the potential of alternative therapies already in development in our laboratory to promote protein chaperoning. We have defined minimal domains necessary for the replacement therapy and identified that HDAC inhibitors have a strong therapeutic potential. For the next year, we will pursue our efforts.

AIM 1. Development of peptide and gene therapies. We have generated a AAV9 carrying a combination of sacsin domains and generated peptides derived from sacsin domains. We will test the efficacy of this vector in resorbing intermediate filament bundles in neurons.

AIM 2. Assessment of therapeutic potential of brain permeant HDAC inhibitors for ARSACS. We will examine the role of different HDACs inhibitors in resorbing intermediate filaments bundles in culture.

Grant: $100,000


Dr. Benoit Gentil, Department of Kinesiology and Physical Education, McGill University
475 Pine Avenue West, room 210, Montreal, Quebec  H3A 2B4

Tel: 514-398-4184 ext 00102