Chapters authored
Cell Therapy in Huntington’s Disease
Huntington’s disease (HD) is a rare neurodegenerative disease inherited in an autosomal dominant pattern. Expanded cytosine-adenine-guanine (CAG) repeats (polyQ) in the huntingtin gene cause the aggregates of abnormally expanded polyQ-containing huntingtin protein, and striatal medium spiny neurons are shown to be the most vulnerable. Affected patients develop cognitive, motor, and psychiatric symptoms typically in middle age, and several pharmacological drugs are currently used for symptomatic relief. Since the effect of current therapies is very limited and there is no way to modify disease progression, there is an unmet need for developing new therapies for HD. Toxin or genetic rodent models are widely used for drug development, and large animal models are also available. Previous studies transplanting cells originating from embryonic or fetal striatal tissues, neural stem cells, mesenchymal stem cells, and induced pluripotent stem cells (iPSCs) in HD animal models have shown the possibilities of clinical trials. Because clinical trials performed using human fetal striatal cells have shown variable outcomes, future directions of cell therapy in HD should consider the reconstitution of a functional dynamic information-processing circuit without ectopic connections. Another major challenge is to achieve controlled differentiation of embryonic stem cells or iPSCs into specific neuronal phenotypes.
Part of the book: Progress in Stem Cell Transplantation