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Trial of Gene Therapy for Parkinson's Disease Successful

Published : 2010-06-22 - Updated : 2017-09-22
Author : Neurologix, Inc.

Synopsis: Neurologix Announces Successful Phase 2 Trial of Gene Therapy for Parkinsons Disease.

Main Digest

Neurologix Announces Successful Phase 2 Trial of Gene Therapy for Parkinson's Disease.

Parkinson's disease is a progressive and debilitating neurodegenerative disorder that arises from the gradual deterioration of nerve cells in the brain. It affects the control of bodily movement and is characterized by four principal symptoms: limb tremor, limb rigidity, bradykinesia (slowness of movement) and postural instability (trouble with balance). Parkinson's disease is a disease of late middle age, usually affecting people over the age of 50. According to the National Parkinson Foundation, 1 million Americans currently have PD, and an estimated 50,000 to 60,000 new cases are diagnosed each year in the United States. Standard therapy for PD often involves use of levodopa, a drug which stimulates production of dopamine. Unfortunately, many patients develop complications from dopaminergic interventions. Alternative treatments include deep brain stimulation, which requires general anesthesia and the implantation of permanent medical devices in the brain.

Neurologix, Inc. has announced positive results in a Phase 2 trial of its investigational gene therapy for advanced Parkinson's disease (PD), NLX-P101. Study participants who received NLX-P101 experienced statistically significant and clinically meaningful improvements in off-medication motor scores compared to control subjects who received sham surgery. In the trial, this benefit was seen at one month and continued virtually unchanged throughout the six month blinded study period. The results also demonstrated a positive safety profile for NLX-P101, with no serious adverse events related to the gene therapy or surgical procedure reported. Patients enrolled in the trial had moderate to advanced PD and were not adequately responsive to current therapies.

Neurologix, Inc., is a clinical-stage biotechnology company dedicated to the discovery, development and commercialization of gene therapies for serious disorders of the brain and central nervous system (CNS). Neurologix's investigational AAV (adeno-associated virus) vector gene therapy, NLX-P101, is a novel, non-dopaminergic approach that uses an inhibitory gene (Glutamic acid decarboxylase or "GAD") to selectively alter the neural circuitry affected in PD and, thereby, normalize brain physiology. Neurologix's technology is the only gene therapy strategy currently in development which bypasses the dopamine system.

"We are extremely pleased that years of research by our group with AAV vector gene transfer technology has led to the unprecedented milestone of a statistically significant improvement in a double-blind, placebo-controlled trial of gene therapy for any neurological disorder," said Michael G. Kaplitt, MD, PhD, scientific co-founder of Neurologix, Inc., neurosurgeon, New York-Presbyterian Hospital/Weill Cornell Medical Center and Associate Professor and Vice Chairman for Research, Department of Neurological Surgery, Weill Cornell Medical College. "We now have solid scientific evidence to support NLX-P101 as an important, potential treatment for this devastating disease."

Matthew J. During, MD, DSc, Professor of Molecular Virology, Immunology and Medical Genetics, Neuroscience and Neurological Surgery, The Ohio State Medical School, and Professor of Molecular Medicine and Pathology, University of Auckland, New Zealand, and Michael G. Kaplitt, MD, PhD, are the scientific founders of Neurologix, Inc., and have been at the forefront of gene therapy research since 1989. This Phase 2 trial is the result of more than 15 years of progress with their work in AAV gene transfer technology. They were the first to demonstrate that AAV could be an effective gene therapy agent in the brain, which they reported in their landmark Nature Genetics paper in 1994. Drs. During, Kaplitt and colleagues subsequently published additional research demonstrating the beneficial effects of AAV-GAD gene therapy for Parkinson's disease in the journal Science in 2002. Today's findings build upon earlier positive results from the NLX-P101 Phase 1 trial, which was the first ever clinical gene therapy trial for Parkinson's disease. Results of that study appeared in 2007 as a cover article in The Lancet and in a second article in the Proceedings of the National Academy of Sciences.

Neurologix and Gene Therapy - A Novel Approach to Parkinson's Disease

In Parkinson's disease, patients lose dopamine-producing brain cells, resulting in substantial reductions in the activity and amount of GABA (gamma-aminobutyric acid), the major inhibitory neurotransmitter in the brain. This contributes to an abnormal increase in activity of the subthalamic nucleus (STN) of the brain, a key regulatory center for movement, and causes a dysfunction in brain circuitry responsible for coordinating movement. GABA is made by a gene called Glutamic acid decarboxylase, or GAD.

Neurologix's gene therapy approach to PD aims to reset the over-active brain cells to inhibit electrical activity and return brain network activity to more normal levels. The strategy involves restoring GABA and thus improving the patient's motor control by using an AAV vector (a disabled, non-pathogenic virus) to deliver the GAD gene back into the STN. Increasing GAD causes more GABA to be synthesized, thus helping to calm the STN over-activity.

NLX-P101 is delivered to the brain through a standard, minimally-invasive surgical procedure that uses similar techniques to those currently employed in traditional surgery for PD. The Neurologix gene therapy procedure, however, does not require general anesthesia nor implantation of a permanent medical device in the brain.

"While dopamine clearly plays a role in Parkinson's disease, dopamine levels in the brain are inherently difficult to control, resulting in sub-optimal treatment outcomes for patients. We believe that by altering chemical targets further downstream in the brain's network that regulates movement, we have the potential to help improve outcomes and restore motor function for patients with advanced Parkinson's disease," added Matthew J. During, MD, DSc, scientific co-founder of Neurologix, Inc.

"Based on this data, we are confident that NLX-P101 has great potential to advance the treatment paradigm for Parkinson's patients, and to eventually offer an important, new therapy for patients with this debilitating disease. The study investigators continue to further evaluate the detailed data and we look forward to its publication or presentation," said Clark A. Johnson, President and Chief Executive Officer of the Company. "Today's news is also important validation for our ongoing development of other technologies for neurological and psychiatric diseases, including our advanced pre-clinical program in epilepsy. Given these results, we would look to pursue a strategic transaction which will maximize value for the Company."

Study Details

This double-blind, multi-center, randomized, sham-procedure-controlled Phase 2 study was designed to evaluate the safety and efficacy of NLX-P101 in patients with moderate to advanced PD who were not well-controlled on available medical therapy. Trial participants were randomized to receive either an infusion of NLX-P101 bilaterally into each subthalamic nucleus, or a sham infusion of a sterile saline solution. Each procedure was carried out under local anesthesia.

The primary measure of efficacy in the study was the difference in off-medication motor scores between the treated and sham groups on the Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 (Motor section), which has long been the standard for clinical assessment in Parkinson's disease. All subjects were evaluated at baseline as well as one, three and six months after undergoing surgery.

The trial also showed that NLX-P101 was well-tolerated with no serious adverse events related to the drug or procedure reported. All treated subjects will continue to be monitored for safety for a 12-month period following their surgical procedure.

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Cite Page: Journal: Disabled World. Language: English (U.S.). Author: Neurologix, Inc.. Electronic Publication Date: 2010-06-22 - Revised: 2017-09-22. Title: Trial of Gene Therapy for Parkinson's Disease Successful, Source: <a href=>Trial of Gene Therapy for Parkinson's Disease Successful</a>. Retrieved 2021-06-25, from - Reference: DW#340-4417.