Title:Recent Progress in Gene Therapy for Parkinson’s Disease
Volume: 12
Issue: 10
Author(s): Y. Nakata, T. Yasuda and H. Mochizuki
Affiliation:
Keywords:
Adeno-associated virus, aromatic L-amino acid decarboxylase, gene therapy, glial cell line-derived
neurotrophic factor, glutamic acid decarboxylase, Neurturin, Parkinson’s disease, neurodegenerative disorder, Akinesia, bradykinesia, dopaminergic neurons, symptomatic molecules, enzymes, neurotransmitter, regenerative proteins
Abstract: Parkinson’s disease (PD) is an age-related and the second most common neurodegenerative
disorder beyond Alzheimer’s disease. A neuropathological hallmark of PD is a prominent loss of dopaminergic
neurons in the substantia nigra projecting into the caudate and putamen. Oral administration of L-dopa and/or
dopamine agonists ameliorates cardinal motor symptoms of PD. However, an intermittent and long-term
treatment with L-dopa frequently induces adverse side effects such as motor fluctuations and dyskinesia. As
alternative therapeutic strategies, the following four approaches are currently under evaluation for clinical gene
therapy trials in PD; 1) recombinant adeno-associated virus 2 system encoding aromatic L-amino acid
decarboxylase (AADC), 2) glutamic acid decarboxylase (GAD) and 3) Neurturin, and 4) equine infectious
anemia virus-based lentiviral system encoding AADC, tyrosine hydroxylase (TH) and GTP cyclohydrolase I
(GCH) in a single transcriptional unit. GAD and Neurturin have been assessed in double blind placebocontrolled
phase II studies; GAD showed a significant improvement in motor function, and Neurturin, although
it failed to show significant effects at 12 months post-treatment, exhibited promising outcomes in additional
examinations at 18 months. The other two approaches also represented significant effects in phase I or I/II
studies. Adverse side effects due to surgery have not been observed. Here, we review preclinical and clinical
trials encouraging further investigations of curative treatment for the patients suffering from PD.
