Induced pluripotent stem cells as a potential treatment for Huntington’s disease

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that usually affects middle-aged individuals, the median age of symptom onset is 42 years. HD is invariably fatal and the drugs that are currently available are only palliative. Of the many promising therapeutic approaches, genetic therapies and especially reintroduction of genetically altered stem cells have gained considerable attention. Studies using stem cell therapies have evolved from using mesenchymal stem cells (MSCs), neural stem cells (NSCs), and embryonic stem cells (ESCs) to induced pluripotent stem cells (iPSCs). Since iPSCs have the ability to differentiate into any of the three mammalian germ layers, their use has become a promising new approach for cell replacement therapy, including their use for treating HD. Two therapeutic approaches using iPSCs for cell replacement include transplantation of undifferentiated iPSCs or using those that have undergone partial differentiation into a desired cell lineage. Very little is known about the relative efficacy of transplanting these two different types of iPSCs, especially with regard to treating HD. This chapter gives a brief overview of stem cell-based transplantation therapy in HD, with a major focus on what is currently known about the efficacy of undifferentiated versus partially differentiated iPSCs transplant therapy in HD. In addition, the novel idea of transplanting reprogrammed (i.e., gene-corrected) autologous cells from HD patients as a source of iPSCs is explored.