Despite extensive research, the underlying causes of neurodegeneration in ARSACS still remain unclear, and thus there is a need for identifying effective therapies for ARSACS patients. My lab over the past several years has focused on characterizing the changes of macromolecular assemblies in ARSACS patients, as well as mapping the ARSACS-linked SACS pathways, to reveal potential drivers of ARSACS. Aberrant alteration of neuronal excitability contributes to increased calcium influx in neurons, which can lead to neurological disorders, including ARSACS. Therefore, identifying molecular targets modulating excitability in human neurons carrying SACS gene mutation in ARSACS patients is a promising first step towards exploring therapeutic interventions. In this newly funded proposal, we will perform a phenotypic screen against annotated compounds in iPSC-derived human neurons carrying the SACS ARSACS mutation to identify molecular targets that restore cellular phenotypes of ARSACS, such as altered neuronal excitability, to the normal state. The role of promising excitability modulators will then be interrogated in ARSACS disease pathogenesis. Identification of drugs acting on targets that modulate abnormal excitability should lay the foundation for future drug development programs for ARSACS.

Grant: $100,000

Duration: one year


Dr. Mohan Babu, Department of Biochemistry University of Regina
3737 Wascana Parkway, Regina,  SK S4S 0A2