[Current status of gene therapy for Parkinson disease]

Abstract

Gene therapy is particularly appropriate for Parkinson disease (PD) since this condition exclusively affects the dopaminergic neurons projecting from the substantia nigra pars compacta (SNc) to the putamen. Currently, 4 ongoing phase I clinical trials are utilizing recombinant adeno-associated viral vectors (rAAv) or lentivirus vectors for the treatment of PD. In this article, we describe recent progress in the development of gene therapy methods for PD by reviewing clinical trials in this field. Parkin-associated PD is recessively inherited, that is, loss of function of parkin leads to the development of parkin -associated PD; hence, substrates for parkin (for its E3 function) are expected to accumulate in the brain. Therefore, the replacement of parkin function in such patients would decrease the toxicity of these substrates. We previously found that the transfer of parkin, encoding a familial PD-linked E3 ubiquitin ligase, in rats with PD could prevent the degeneration of nigral dopaminergic neurons. In addition, we recently reported the case report of a preclinical examination of rAAV vector-mediated retrograde delivery of parkin into nigrostriatal dopaminergic neurons in a non-human primate. In this article, we also review the potential of parkin gene therapy for the treatment of PD patients.