Gene therapy for Parkinson's Disease produced significant improvements in motor function and significant decreases in abnormal brain metabolism in a phase I study, reported investigators at the annual symposium of the Parkinson Study Group here.


In the 12-patient dose-escalating trial, patients who received gene therapy delivered via a catheter unilaterally to the subthalamic nucleus (STN) had a statistically significant 27% (p=0.4) improvement at 1 year in motor function in the side of the body contralateral to the treated hemisphere, as measured on the Unified Parkinson's Disease Rating Scale.


In addition, fluorodeoxyglucose-enhanced positron emission tomography (FDG-PET) studies at 1 year revealed a decrease in abnormal brain metabolism in the treated hemisphere, and an increase in metabolic abnormalities in the untreated hemisphere.


Patient self-ratings on an activities of daily living scale showed a trend toward improvement, but this trend was not statistically significant, reported co-investigator Andrew Feigin M.D., associate director of the Movement Disorders Center at North Shore-Long Island Jewish Health System in Manhasset, New York.


"The goal of this research is to determine whether we can 're-set' a specific group of cells that have become overactive, causing the characteristic impaired movements associated with Parkinson's disease," said senior investigators Michael G. Kaplitt, M.D., Ph.D. and Dr. Matthew J. During. "The interim UPDRS scores are highly promising and, if they are borne out with additional data, would be comparable to results seen with STN Deep Brain Stimulation. Unlike deep brain stimulation, however, our gene therapy approach is much simpler, can be carried out entirely under local anesthesia, and avoids leaving any devices in the body."


Drs. Kaplitt and During are co-founders of and consultants to Neurologix, the company that developed the gene-therapy technique. Dr. Kaplitt is a clinical scholar in neurosurgery at Weill Cornell Medical College in New York City. Dr. During is Professor of Molecular Medicine at the University of Auckland in New Zealand.


The therapy uses adeno-associated virus (AAV) as a vector to carry into the brain the gene that encodes for glutamic acid decarboxylase (GAD), the enzyme that synthesizes the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).


The study results come a little more than a decade after Drs. Kaplitt and During first demonstrated that AAV could be a safe and effective vector for delivery of a target gene to the brain.

The Phase I trial, the first FDA-approved clinical trial of gene therapy for PD is an open-label dose-escalation study involving 12 patients with severe PD of at least five-years duration that is refractory to currently available medical therapies. {CLICK FOR MORE}