This consortium aims to capitalize on an unprecedented """"""""grand"""""""" opportunity to develop a novel and powerful model of Huntington's disease (HD), a fatal neurodegenerative condition with no current treatment. Skin cells from patients with HD can be reprogrammed to pluripotency and then differentiated into specific neuronal and glial cell types, permitting investigation of the effects of the genetic lesion in the susceptible human cell types. We hypothesize that the genetic changes that cause HD lead to specific alterations in neuronal function- perhaps even survival-that will give important clues as to the mechanism and progression of disease. Altered cellular phenotypes will also serve as the foundation for translational research and drug development. Stimulus funding will bring together a highly focused group that (i) has a strong track record of innovative HD research and of working together, (ii) is poised to engage in cutting-edge research with recently generated induced pluripotent stem (iPS) cells derived from HD patients and is committed to broad distribution of findings, protocols and iPS lines, (iii) can capitalize on this stimulus funding through further grant applications and collaborative studies, and (iv) is partnered with CHDI, an HD foundation with dedicated HD stem cell and translational/drug discovery programs. This infusion of funds will accelerate the coordinated analysis of iPS lines and leverage the complementary, synergistic skill sets that will move the field forward more rapidly than would be possible by any group alone. The proposed studies will provide an entirely novel genetically accurate model to test new drugs in the fight against this disease, a unique resource that will benefit the entire HD community.
We hypothesize that the genetic changes that cause Huntington's disease lead to specific alterations in neuronal function-perhaps even survival-that, in turn, give important clues as to the mechanism of disease and its progression and offer a potential basis for small molecule screening assays. Our studies will provide a more authentic way to study the consequences of the HD mutation in human target cells. They represent a unique and timely opportunity to enhance the investigation of disease mechanisms and will generate a validated resource freely available to the HD community to further accelerate HD research toward a successful treatment.
