The Sacs knock-out (KO) mouse is a faithful model of ARSACS, displaying ataxia, muscle weakness, cerebellar degeneration, and, as we have recently shown, learning and memory deficits. With this proposal, we seek to pharmacologically rescue motor- and cognitive phenotypes in the Sacs KO model of ARSACS with a drug that raises levels of a second messenger (cAMP) in the brain and that is currently in phase 2 and phase 3 clinical trials for two neurodevelopmental disorders. Second, we propose to develop gene therapy for ARSACS. Third, we have generated a conditional Sacs KO model, which we will use to pinpoint where and when Sacs loss-of-function causes the spectrum of ARSACS symptoms.
Grant: $100,000
Duration: one year
Dr. Stefan Strack, Department Neurosciences @Pharmacology
University of Iowa Carver College of Medicine
2-452 BSB, 51 Newton Rd. Iowa City, IA 52242
stefan-strack@uiowa.edu
Contact: stefan-strack@uiowa.edu