study design

DYT11, or myoclonus-dystonia (M-D), is a genetic movement disorder characterized by muscle contractions, myoclonus, and psychiatric symptoms. Current treatments provide limited relief, with deep brain stimulation only available after pharmacological options are exhausted. This study aims to understand how the loss of ε-sarcoglycan in dopaminergic neurons contributes to M-D symptoms, which could lead to new therapeutic approaches targeting the dopaminergic system​.

hypothesis

Loss of ε-sarcoglycan in dopaminergic neurons leads to dopamine system dysfunction, resulting in myoclonus-dystonia. Additionally, dopaminergic-targeting drugs may effectively alleviate M-D symptoms in DYT-SGCE patients.

study design

Aim 1: Develop and analyze dopaminergic neuron-specific Sgce conditional knockout (dKO) mice to test the hypothesis that the selective loss of ε-sarcoglycan induces myoclonus through cell-autonomous mechanisms.

Aim 2: Test a promising dopamine-targeting drug, VU6021625, in Sgce knockout mice to assess its potential to reduce myoclonus symptoms

impact on dystonia treatment

This research could identify dopaminergic dysfunction as a primary driver of DYT-SGCE, offering a novel treatment pathway. Successful outcomes from the drug testing may lead to clinical trials and provide patients with an effective therapy targeting the underlying mechanisms of DYT11​.

next steps for development

Completion of this study will provide critical data for an NIH R01 grant submission. Future work will expand upon findings related to dopaminergic involvement in M-D to refine and validate therapeutic targets

additional information

The $40,000 budget includes support for personnel, mouse care, and laboratory supplies. Dr. Hong Xing, as co-investigator, and research technician Pallavi Girdhar, will assist with experiments, data collection, and animal management.

collaboration

Dr. Yuqing Li, the lead investigator, brings extensive expertise in the pathophysiology of movement disorders. Collaborators Dr. Hong Xing and Ms. Pallavi Girdhar will contribute to the project’s execution through behavioral analysis and animal care. Together, this team provides comprehensive expertise in genetic modeling and experimental analysis in dystonia research​