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Project

A genetic-valid and phenotypic-valid mouse model to define when, where and how to treat dystonia

Isolated dystonia is an incurable neurological movement disorder. It is the disease where abnormal involuntary movements occur despite normal brain structure and neurochemistry. It is poorly appreciated despite being the third most common movement disorder and its painful, debilitating symptoms that prevent everyday activities. It has been challenging to identify why dystonia develops. A major roadblock is that human genetic causes of dystonia do not cause movement dysfunction in animal models. Our new data now overcome this. We show a genetic human dystonia mutation that causes a dystonia-like disorder in mice. These “dystonia” mice even mimic the childhood-onset and partial penetrance of the human disease. Further, we identified a biochemical defect that appears to drive the dystonia and is a feasible target for small molecules. This proposal exploits this breakthrough to solve several fundamental questions about dystonia. When is the brain is vulnerable to dystonia; is this only in development? Can dystonia be reversed, or is it permanent once symptoms occur? Which brain regions are involved, and do these contain “micro” pathology to explain symptoms. In parallel, we simultaneously assess the usefulness of the novel therapeutic target and test this at different disease stages.

Date:1 Jan 2020 →  31 Dec 2023
Keywords:Isolated dystonia, “dystonia” mice
Disciplines:Neurological and neuromuscular diseases, Lipids, Genetics