11 - Gene and Cellular Transplantation Therapies for Huntington's Disease

Abstract

Huntington's disease is a genetic disorder inherited in an autosomal dominant manner. The disease is caused by a mutation manifested in the IT15 or huntingtin gene located on chromosome 4. The devastating and incurable symptoms of HD include cognitive, motor and psychiatric disturbances. The cognitive symptoms often present years before the other signs and include deficits in executive functions, procedural memory and psychomotor skills. Unfortunately no efficient therapy exists that can tackle all of these symptoms while at the same time delaying or preventing cell death. Cell death in HD occurs predominantly in the projection neurons of the striatum, and it is this population of neurons that most therapies focus on protecting. However, cortical degeneration also plays a prominent role in the manifestation of deficits in higher order cognitive functions and must be targeted while designing a therapy. The discovery of toxin-induced and genetic models in both rodents and nonhuman primates has allowed for the comprehensive testing of therapies before they reach the clinic. Pharmaceutical therapies are currently the most commonly used to treat HD patients. These may be efficient at temporarily tackling the symptoms of HD but do not address the inevitable disease progression. There are a few neuroprotective therapies currently in clinical trials, but they are somewhat limited in their effectiveness. Cell replacement strategies are also in use but have been shelved in the past few years due to lack of proper funding. This review will discuss neuroprotective gene therapies and restorative cell transplantation therapies that are in use for HD research and therapy.