Huntington's Disease Team
Huntington's disease (HD) is a devastating degenerative brain disease with a 1 in 10,000 risk of having a mutation that inevitably leads to death. These numbers do not fully reflect the large societal and familial cost of HD, which requires extensive caregiving. HD has no effective treatment or cure and symptoms progress without stopping for 15-20 years, with onset typically striking in midlife. Because HD is genetically dominant, the disease has a 50% chance of being inherited by the children of patients. Symptoms of the disease include uncontrolled movements, difficulties in carrying out daily tasks or continuing employment, and severe psychiatric manifestations including depression. Specific regions of the brain are severely affected, most notably the striatum. Current treatments only treat some symptoms and do not change the course of the disease, therefore a completely unmet medical need exists. Human embryonic stem cells (hESCs) offer a possible long-term treatment that could relieve the tremendous suffering experienced by patients and their families. HD is the 3rd most prevalent neurodegenerative disease, but because it is entirely genetic and the mutation known, a diagnosis can be made with certainty and clinical applications of hESCs may provide insights into treating brain diseases that are not caused by a single, known mutation. Trials in mice where protective factors were directly delivered to the brains of HD mice have been effective, suggesting that delivery of these factors by hESCs may help patients. In addition, transplantation of fetal brain tissue in HD patients suggests that replacing neurons that are lost may also be effective. While encouraging, the ability to differentiate hESCs into neuronal populations offers a powerful and sustainable alternative for cell replacement. Further, hESCs offer an opportunity to create cell models in which to identify earlier markers of disease onset and progression and for drug development.
A core group of HD and stem cell experts together with clinicians experienced in stem cell and HD clinical trials have been assembled by the PI to initiate the planning process for a hESC-based therapeutic trial for HD within four years. While feasible, in order for the potential of hESCs in HD to be realized, a very forward thinking disease team effort will allow the most experienced investigators in HD, stem cell research and clinical trials to come together and determine the best way to treat the disease. This planning grant would allow for these interactions to occur in a structured and consistent manner. The planning award will be used to identify critical gaps in our knowledge, available technology, and areas of expertise that need to be addressed prior to moving hESC-based therapy for HD into the clinic. Because the work proposed would entail the use of non-NIH approved hES cell lines, it would be ineligible for Federal funding.
Leslie Michels Thompson
University of California, Irvine
Disease Team Planning