Cell-based therapies for Huntington's disease

HD is an inherited single-gene dominant disorder caused by the abnormal expansion of CAG repeats in the HTT gene [1,2]. Excessive aggregation of mHTT proteins cause cell toxicity and apoptosis of the GABAergic projection neurons in the striatum and some glutamatergic neurons in the cortex [3]. Currently, there is no cure for HD. Efforts have focused on symptomatic treatment with drugs or gene therapy. The objective of gene therapy is to reduce the translation of toxic mHTT proteins through RNAi. To be most effective, RNAi treatment strategies need to be applied at the early stages of the disease; however, most patients do not develop symptoms and are not found to have the disease until severe degeneration of striatal neurons has already occurred. An alternative treatment is cell-based therapy, which replenishes the lost population of striatal neurons by transplanting neural cells intracranially into the striatum. In this review, we highlight new findings in gene and cell-based therapy within the past 2 to 3 years. We also discuss a combination approach that could be used to overcome the limitations of each individual technique, thus offering a more comprehensive therapy for HD.