Dystonia is characterised by involuntary movements, abnormal posturing and twisting of one or more parts of the body. It can start at any age but typically young onset is associated with severe symptoms. There is no cure for dystonia, but treatments can improve symptoms and include pharmacological therapies, botulinum neurotoxin (BoNT) and the deep brain stimulation (DBS). Unfortunately, not all patients respond and DBS is only eligible for selected cases.

The cause of dystonia is still unknown and research suggests it is a problem of the brain networks controlling movement, leading to excessive muscle activation, which involves both environmental and genetic factors. The neurons do not die as they do in Parkinson’s disease, but have a functional problem. The commonest genetic form of dystonia was discovered twenty years ago. A mutation in the TOR1A gene, (DYT1) was proven to be the cause. This change is associated with severe generalised dystonia usually starting in childhood or adolescence. This mutation deletes 3 letters of the DNA code and translates to an abnormal protein which does not work properly in neurons. However, the DYT1dystonia has an extra challenge. The presence of this mutation does not always lead to developing dystonia, and only 30% of the patients having this mutation will develop symptoms.

At the Reta Lila Weston Institute laboratories, we use the latest stem cell technology in DYT1 patients with the aim studying the stem cells and brain cells which express abnormal torsinA protein and its relationship with other proteins that can contribute to dystonia. We reprogrammed cells from skin biopsies from patients with DYT1 dystonia and control individuals to stem cells. We are then able to derive iPSC cultures of these cells into neurons. Our research is focused on identifying the distinct patterns of gene expression in neurons between patients with the DYT1 mutation and controls who do not have the mutation. We also will look at those people with the mutation who have not developed dystonia.  We hope that our research will help to understand key factors of the disease.