We have seen some encouraging research and clinical trial work with a number of gene and cell-related technologies including Spheramine, CERE-120 and GDNF, although GDNF trials are not currently ongoing. We suspect a combination of these treatments will eventually offer vast improvements to people with Parkinson's disease. We hope they are also precursors to a cure.
The study being published in The Lancet used an adeno-associated virus (AAV) vector to deliver an inhibitory gene (glutamic acid decarboxylase or GAD) to the subthalmic nucleus (STN) of the brain. In Parkinson's disease, STN activity is abnormally increased, due to a deficit in GABA (gamma-aminobutyric acid), the major inhibitory neurotransmitter in the brain. Increasing GAD causes more GABA to be synthesized, calming the STN over-activity. The value of this strategy has been demonstrated in previous human studies where reducing STN activity by either electrical stimulation or lesioning helps ameliorate the symptoms of advanced Parkinson's disease.
The phase one study was not specifically designed to assess efficacy. Nonetheless, the researchers reported the clinical outcomes to be encouraging. Patients showed significant improvement in both the "on" and "off" states of their illness (the time periods in which they achieve or do not realize benefit from drug therapy) beginning at three months following surgery and continuing through the end of the study. These improvements occurred predominantly on the side of the body corresponding to the side of the brain receiving treatment. Moreover, the absence of change at the earliest time point following treatment suggests that the improvement was not likely due to the surgical lesioning of the targeted brain region, as surgical approaches typically give rise to immediate, short-lasting benefit around the time of surgery, while prior studies of AAV-mediated gene therapy show that gene expression gradually increases to a maximal level over a period of weeks.
If you would like to read the article from The Lancet, just follow this link to the article "Gene therapy for Parkinson's disease".
Another good article from 2003 is "First Parkinson's Gene-Therapy Patient Keeps Faith" from Reuters and Yahoo! News. It relates the experience of one of the 12 patients who participated in the phase one clinical trial.
Now researchers and the sponsoring company Neurologix are looking forward to launching a phase two clinical trial where they will double-blind the patients. This study will show if patients receiving the Parkinson's gene therapy GAD improve more than patients who undergo a sham surgical procedure.
