Parkinson’s disease is a progressive neurodegenerative disease that usually develops at 40–70 years of age, with major signs of dyskinesia including tremor, hypokinesis, muscle rigidity, and postural reflex disorder. It affects about 140,000 patients in Japan. Previously, it was thought to affect far fewer patients in Japan than in Western countries, but a recent study has revealed very similar incidences. This may reflect the aging population in Japan. The disease progress differs among patients, and the time from development to severe disability ranges from 3 to 15 years.
The cause of Parkinson’s disease is still unknown, despite extensive studies. Genetic mutations have been found in some familial Parkinson’s disease cases, but the mechanism of nerve cell degeneration is unknown. No specific mutation has been identified in sporadic Parkinson’s disease, which accounts for about 90% of all cases. Therefore, a radical treatment for Parkinson’s disease has not yet been developed.
GTRI is pursuing a novel gene therapy for Parkinson’s disease that recovers the dopamine production capacity of nerve cells that remain in the putamen. This is achieved by introducing the gene encoding an enzyme involved in dopamine synthesis (AADC) into nerve cells.
In 2007, a clinical trial in which an AAV vector expressing AADC was administered to the bilateral putamen was performed at the Jichi Medical University. It was performed in a small number of patients to confirm its safety. Patient motor symptoms successfully improved after 6 months. PET imaging using a protein that binds to AADC as a tracer revealed continuous AADC expression at the vector injection site, even 5 years after the transgene procedure.