Grant: Fellowship - Priority Announcement: Huntington's Disease

To date, the problem in Huntington's disease (HD) has been thought to be due to nerve cells producing their own, genetically coded for, abnormal mutant huntingtin protein (mHtt), which then causes them to dysfunction and die. In recent years, there has been evidence to suggest that other cells, such as those involved in inflammation, may also contribute to the loss of neuronal cells. However, such cells have only been thought of as having indirect effects and not central to the disease process. Recently, though, we have found in HD patients - who were transplanted with fetal tissue designed to replace cells lost to the disease process - that the abnormal mHtt could be seen in the transplant. This mHtt could only have got into the transplant from the patient as the grafted tissue was from unaffected donors. This unique observation forms the basis of this application as we now investigate the theory that mHtt can be transferred between cells from circulating immune cells that can get into the brain via leaky blood vessels. If true, this new theory would have wide ranging implications for HD, and similar diseases, and bring with it a totally new therapeutic approach to this currently incurable condition.