The dystonias are a group of movement disorders characterised by involuntary sustained or repetitive muscle contractions, leading to uncontrollable twisting movements, postures or tremor of the affected body parts. They encompass childhood-onset dystonias that are usually genetic in origin through to adult-onset focal dystonias affecting one of part the body. Dystonia results from dysfunction, not death, of brain cells, leading to defects in the brain circuits that control voluntary movement. Studies suggest that the cellular mechanisms that are dysfunctional may be shared across multiple different forms of dystonia.

The commonest form of childhood-onset dystonia (known as DYT1 dystonia) is due to a single mutation of the TOR1A gene. DYT1 dystonia has been studied in cell and animal models, and a number of changes in the neurons (brain cells) have been identified, though it is not understood how these neuronal changes disrupt the brain circuits. This project aims to use stem cell technology to study neurons derived from the skin cells of patients with DYT1 dystonia, as well as neurons from a mouse model of DYT1 dystonia. We aim to delineate the main cellular features that are common across these models of DYT1 dystonia. The ultimate goal is to develop a panel of cell markers that reliably reflect the neuronal dysfunction that occurs in DYT1 dystonia. This will then form the basis of experiments to manipulate normal and abnormal TOR1A gene expression and reverse these changes. This panel of disease-relevant cell markers could then be used to screen for compounds that can similarly reverse these cellular changes, thereby becoming a springboard for drug discovery and development of new treatments for DYT1 and possibly other forms of dystonia.