An experimental treatment using gene therapy appears to have improved the symptoms of patients with advanced Parkinson's disease.
The small study, involving just 45 patients, is the first successful trial to compare gene therapy to a sham surgical procedure. It's also the first to show positive results with the use of gene therapy in Parkinson's patients.
Gene therapy is a still experimental field of study that involves inserting genes into tissues, in hopes of replacing faulty genes or boosting beneficial genes.
In this study, researchers focused on a gene that controls production of an enzyme called GAD (glutamic acid decarboxylase).
GAD controls a neurotransmitter called GABA, which calms overactive neurons. Parkinson's patients no longer properly produce GAD, resulting in the tremors and muscle stiffness that mark Parkinson's.
For the study, published online Thursday in the journal Lancet Neurology, researchers inserted into the patients' brains a harmless virus engineered to release billions of copies of GAD.
Sixteen patients received the therapy, while 21 others received a sham operation. Patients who got the sham treatment had "burr holes" drilled halfway into their skulls and saline injected, to trick them into thinking they were getting the real therapy.
The patients were aged between 30 and 75, and all had moderate to advanced Parkinson's with symptoms that were not adequately controlled with the usual medications.
After six months, those who received the real gene therapy scored 23 per cent better on a standard test to measure motor skills. Interestingly, those who got the sham operation also did better, though not as well: about 13 per cent better.
Improvements in motor control were seen at one month and continued virtually unchanged for the six-month observation period.
Side effects were mild, with the most common being headache and nausea.
"The treatment was remarkably well tolerated, with mostly only mild adverse events in the AAV2-GAD treated group that were felt to be unrelated to the treatment, and completely resolved," Dr. Andrew Feigin, the study's lead author and associate professor of neurology and molecular medicine at the Feinstein Institute for Medical research in Manhasset, New York, said in a statement.
The researchers say it's unclear whether the gene therapy caused an increase in GABA; if it did, they said it is not clear how long the genes will pump out GAD to control the GABA neurotransmitter.
The study was paid for by Neurologix Inc., the biotechnology company that devised the therapy. One of the study's authors, Dr. Michael Kaplitt, a neurosurgeon at New York-Presbyterian Hospital and Weill Cornell Medical Center, is a company co-founder and holds stock options. Many of the other authors reported ties to Neurologix and other pharmaceutical companies.
In an accompanying commentary, Dr. Michael Hutchinson of New York University School of Medicine questioned whether gene therapy offers any advantages over deep-brain stimulation, which has been used to treat Parkinson's disease for about a decade.
Feigin told WebMD the answer to that is not yet clear.
"Even if this proves to have comparable or even near-comparable efficacy to DBS, I would think that it might still have a place in treatment," he said. "Most importantly, this study shows this kind of therapy can be done safely."
