Neural transplantation in patients with Huntington's disease.

The gene for Huntington's disease was identified in 1993 as being a CAG repeat expansion in exon 1 of a gene now known as huntingtin on chromosome 4. Although many of the downstream effects of this mutant gene were identified in the subsequent years, a more detailed understanding of these events will be necessary in order to design specific interventions to interfere with the disease process and slow disease progression. In parallel, a number of groups have been investigating alternative approaches to treatment of Huntington's disease, including cell and tissue transplantation. As the brunt of cell dysfunction and loss is borne by the striatum, at least in the early to mid-stages of disease, the goal is to identify methods for replacing lost cells with fetal neuroblasts that can develop, integrate into the host circuitry and thereby restore lost function. Clinical studies in which primary fetal neuroblasts were transplanted into the brains of patients with advanced Parkinson's disease have demonstrated benefit when the transplant methodology closely follows the biological principles established in animal experiments. On the basis of demonstrated benefit following striatal cell transplantation in animal models of Huntington's disease, a small number of studies have now commenced in patients with Huntington's disease. To date, these clinical studies have demonstrated the feasibility and safety of transplantation in this condition, but it will require several more years yet before the efficacy of the procedure can be confidently established.