Parkinson's gene therapy shows success in humans

A gene therapy for Parkinson's disease has shown promise in early stage clinical trials.

According to treatment developer Neurologix, Inc. , the 12-patient Phase I trial is the world's first study to use a viral vector for the treatment of an adult neurological disease.

A Neurologix news release reports:

[T]he vector was injected into a specific target site in the brain in order to transfer a gene to treat Parkinson's disease. The gene encodes glutamic acid decarboxylase (GAD), an enzyme which synthesizes the major inhibitory neurotransmitter in the brain, (gamma)-aminobutyric acid (GABA).

Under the FDA-sanctioned trial protocol, patients with advanced Parkinson's disease received unilateral (one side of the brain) infusion of AAV-GAD via a hair-thin catheter into the subthalamic nucleus (STN), a deep brain structure known to function abnormally in Parkinson's patients. According to the interim findings, Neurologix's STN AAV-GAD treatment appears to be safe and well-tolerated in advanced Parkinson's disease, with no evidence of adverse effects or immunologic reaction related to the study treatment. Furthermore, patients in the trial, at one year, exhibited a statistically significant improvement (27%, p = .04) in motor function on the side of their body correlating to the treated part of the brain, as measured by the Unified Parkinson Disease Rating Scale (UPDRS). In contrast, the untreated side evidenced no significant improvement in the UPDRS score. Also, activities of daily living (ADL), another standard measure of Parkinson's severity which is recorded by the patients themselves, showed a strong trend toward statistical improvement (p= .06).

In addition, fluorodeoxyglucose (FDG)-PET scans at one year revealed that the treated side of the brain exhibited a statistically significant decrease in abnormal metabolism, while the untreated side showed a further increase in abnormal metabolism. The imaging results were considered similar to those achieved with STN Deep Brain Stimulation, an FDA-approved treatment which currently represents the preferred surgical approach for advanced Parkinson's disease. This data provides solid biological support for the observed clinical improvements.

The research was presented at the 19th Annual Symposia on the Etiology, Pathogenesis and Treatment of Parkinson's Disease and Other Movement Disorders.

In a statement, Neurologix cofounders Michael G. Kaplitt and Matthew J. During commented: "While the primary objective of any Phase I trial is to demonstrate safety, the FDA's requirement of unilateral infusion of AAV-GAD allowed us the unique opportunity to compare treated and untreated sides of the brain. In essence, the untreated side acted as a control. The combined clinical and imaging data provide powerful evidence that this treatment appears to be efficacious, as well as safe, at the current dose levels."

Pending final results from the Phase I study, Neurologix plans to submit to the FDA a pivotal trial protocol for using the treatment approach for Parkinson's.