The goal of this project is to develop therapeutic interventions that would ameliorate the
degeneration of neurons in ARSACS.
1. Test compounds that enhance mitochondrial motility in rat hippocampal neurons to determine if they also
enhance motility in sacsin -/- mouse neurons.
2. Establish conditions for cultured sacsin-/- neurons that will provoke the formation of neurofilament
aggregates seen in vivo in older sacsin -/- mice and determine if those aggregates impeded proper
transport of mitochondria.
3. Test compounds that enhance mitochondrial motility to determine if they can restore normal levels of
mitochondrial transport in the presence of neurofilament aggregates.
4. Determine if the NMNAT/SARM pathway is involved in the degeneration and death of neurons in vivo in
sacsin -/- mice.
Duration: one year
Dr. Thomas L. Schwarz, Professor, F.M. Kirby Neurobiology Center Children’s Hospital, Boston Children’s Hospital CLSB12-130
Harvard Medical School CLSB 12-130, 3 Blackfan Street, Boston, MA 02115
Tel:(617)-919-2219 (office) or (717)-919-2271(fax)