Parkinson's disease yields to experimental gene therapy

A small-scale gene therapy trial conducted at seven U.S. medical centers has found that a single infusion of a specialized gene, piggybacked onto a virus and fed directly into the brain, can safely lessen the severity of symptoms and improve response to medication in patients with advanced Parkinson's disease.

The clinical trial -- the results of which were published Wednesday in the journal Lancet Neurology -- marks the first time that gene therapy has demonstrated effectiveness in treating Parkinson's in humans when compared with a "sham" treatment.

The Phase 2 study of a gene therapy for Parkinson's, designed largely to gain a clearer picture of a treatment's safety, also yielded promising results on that front: Among 16 subjects who received a copy of the glutamic acid decarboxylase, or GAD, gene directly into their brain's subthalamic nucleus, the most common drug-related side effects were headache and nausea. While one subject who got the active gene therapy developed a bowel obstruction, researchers concluded it was unrelated to the treatment.

The GAD gene is thought to regulate the production of a neurochemical called GABA, which is underactive in some parts of the brain and overactive in others, resulting in tremors, irregular gait, language and cognitive problems, and difficulty in initiating movement. While patients with the disease often respond well to drugs that compensate for those imbalances, those drugs lose effectiveness over time.

The findings are a step forward for the promising but troubled field of gene therapy. Researchers and regulators have wrestled with widespread concern that gene therapy could prompt irreversible immune responses, cause unanticipated gene mutations or exert effects beyond the intended target. But those concerns did not seem to materialize in the course of the study, which was funded by the New Jersey company Neurologix, which developed the technique of delivering the GAD gene and hopes to market the therapy.

Compared with 21 subjects who were given a surgical infusion of a saline solution into the brain, the 16 subjects who had a copy of the GAD gene fed into both sides of the subthalamic nucleus showed significantly greater improvement on an overall measure of disease severity. While those in the placebo arm of the study did see improvements in the severity of their symptoms, those on gene therapy improved more dramatically at one month, three months and six months after they had the surgery. And while half of the 16 subjects who got the gene therapy improved by nine points on a comprehensive measure of Parkinson's severity, just three of the 21 subjects who got the sham surgery (14%) made such an improvement.