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Gene therapy for Parkinson's disease: from non-human primates to humans.

Gene therapy strategies in non-human primate models of Parkinson's disease (PD) are beginning to produce results consistently, and have been successfully translated to clinical trials. Although not all of the therapeutic efforts based on gene therapy have demonstrated clinical efficacy, the stereotactic techniques and at least three different beneficial genes that have been delivered to patients have been proven to be safe. The adeno-associated virus has been used as an effective and safe delivery vehicle for the first three, single therapeutic transgenes (ie, glutamic acid decarboxylase, aromatic l-amino acid decarboxylase, and neurturin) to be tested in trials. In addition, the larger lentivirus, which has been used for the codelivery of up to three therapeutic genes in parkinsonian non-human primates, has also being used in a trial in humans. Additional preclinical and clinical research is required to advance the understanding of PD and its potential treatments. Gene therapy, however, has the potential to be a safe and effective therapeutic option for an increasing number of patients with PD in the near future. In this review, the pertinent scientific research related to the use of gene therapy for the treatment of PD is summarized, with a particular focus on the accomplishments and challenges during the past 2 years.