Dystonia

Dystonia is characterized by involuntary movements due to excessive or exaggerated muscle activity. The movements depend on the strengths and patterns of muscles involved. In its mildest form, dystonia may appear merely as an exaggeration of an otherwise normal movement. In more serious cases, movements are twisting, stiff, and slow. In its most severe forms, dystonia is characterized by persistent involuntary posturing. Dystonia can occur alone or as a symptom of many other disorders. Although dystonia affects many people, we are just beginning to understand the neurobiological causes.

What brain regions are implicated?
Dystonia traditionally is associated with dysfunction of the basal ganglia, but recent studies have implicated abnormal cerebellar function too. These new studies have led to the concept that dystonia is a motor circuit disorder. Our work focuses on understanding how this circuit gets disrupted. [Refs]

What neurotransmitters and cell signaling pathways are abnormal? 
Some forms of dystonia are linked with dysfunction of dopaminergic pathways, while other studies have revealed dysregulation of cellular calcium homeostasis. Understanding common underlying mechanisms will provide insight into many forms of dystonia. [Refs]

What can animal models teach us about human dystonia?
Why are females more often affected than males? Why does stress make dystonia worse? What genes contribute to the expression of dystonia? We use mouse models to help us answer these questions, and have an interest in developing monkey models. [Refs]

Can we identify promising new treatments?
Our anti- dystonia drug discovery program is aimed at identifying new treatments for dystonia, using a screening program based on animal models. [Refs]

How does dystonia affect people?
We are conducting clinical and translational studies that include documenting natural history and co- morbidities in humans with dystonia, collecting samples for a biorepository for genetic and other biomarker studies, and developing the best designs for clinical trials. [Refs]