New Model Explores Role of Cerebellum in DYT1 Dystonia


The basal ganglia and cerebellum are brain structures that regulate motor movement and motor learning. A balance between these two systems allows for smooth, coordinated movement. Dystonia can occur in humans when either system is disrupted or damaged. Researchers have been increasingly interested in clarifying the role of the cerebellum in dystonia and what that might mean for novel therapies. Researchers led by past DMRF Medical & Scientific Advisory Council Member Dr. Kamran Khodakhah at Albert Einstein College of Medicine have demonstrated in mouse models that the cerebellum is the main site of dysfunction in DYT1 dystonia. DYT1 dystonia occurs when a protein in the brain called TorsinA becomes mutated and fails to function normally. Dr. Khodakhah’s team created a new mouse model to explore the effects of TorsinA in dystonia. Reducing the amount of TorsinA in the cerebellum of these mice induced dystonia symptoms. Intriguingly, reducing the amount of TorsinA in the basal ganglia of these mice did not produce dystonia symptoms. When these experiments were conducted in juvenile mice, the animals showed no symptoms, suggesting the young mice were able to compensate for the TorsinA loss.

The investigators found that the loss of TorsinA function caused the cerebellum to generate faulty output signals. They propose the downstream effect of these faulty signals from the cerebellum could ultimately disrupt basal ganglia function. Future studies in this mouse model could help clarify the precise changes in the cerebellum induced by failure of TorsinA and point toward new treatment strategies for DYT1 and other inherited dystonias.

The DMRF previously reported on work from Baylor College of Medicine that also produced intriguing insights regarding the cerebellum and dystonia.

Fremont R, Tewari A, Angueyra C, Khodakhah K. A role for cerebellum in the hereditary dystonia DYT1. eLife. 2017; 6: e22775.

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