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.
Financement: 100 000$
Durée: un an
Dr Stefan Strack
Dept. Neuroscience & Pharmacologie
University of lowa Carver College of Medicine
2-452 BSB, 51 Newton Rd.
lowa City, IA 52242 USA
Coordonnées:Stefan-strack@uiowa.edu