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. Our laboratory is moving forward the development of a gene therapy and focused on the Development of peptide and gene therapies. We have generated a AAV9 carrying a combination of sacsin domains and generated peptides derived from sacsin domains and will obtain proof of principle of efficiency. Our lab is also working on finding other therapeutic strategies and we are assessing the therapeutic potential of brain permeant HDAC inhibitors for ARSACS. We will examine the role of different HDACs inhibitors in resorbing intermediate filaments bundles.
Duration: One year
Dr. Benoit Gentil & Dr. Heather Durham
Department of Kinesiology and Physical Education, McGill University
475 Pine Avenue West, room 210, Montreal (Québec) H2W 1S4
email: firstname.lastname@example.org, email@example.com