Neurologix, Inc. (OTC Bulletin Board: NRGX),today 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 overactive 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.
Tuesday, June 22, 2010
Thursday, June 10, 2010
Parallel brainstem circuit discovery suggests new path in Parkinson's research
By Paul Francuch
Chicago and Montreal researchers studying the lowly lamprey eel have identified an overlooked nervous system pathway running parallel to known brainstem locomotor command circuitry in vertebrates such as birds, fishes and mammals.
The finding is reported in Nature Neuroscience, online May 16, and highlighted in the magazine's "news and views" section.
Simon Alford, University of Illinois at Chicago professor of biological sciences and the article's corresponding author, said the role of a neurotransmitter associated with this parallel pathway may also suggest new research directions for treating Parkinson's disease.
Alford, along with his former graduate student and lead author Roy Smetana, now a University of Pittsburgh resident in psychiatry, worked with Université de Montréal and Université de Québec à Montréal neurobiologist Réjean Dubuc and his post-doctoral researcher Laurent Juvin in trying to sort out how the neurotransmitter analog muscarine modifies sensory information going to the brain.
Their work determined that muscarine stimulated neural activity, leading to locomotion in the laboratory lampreys.
The group focused its attention on a collection of brainstem neurons that tell the spinal cord to generate motor output that enables walking and other locomotion.
"We started looking at this group of neurons, which in the lamprey are conveniently very large, so they're easy to plant electrodes and record from," said Alford. "We discovered the muscarinic excitation was not working on these cells, but on a previously unknown group of cells within the brainstem."
What's more, these newly discovered brainstem neurons showed what Alford called a "very odd response" to the muscarine.
"Instead of just turning on -- like a synapse turns on a neuron and makes it fire -- when you put muscarine on these cells, they turn on and stay on" for a minute or longer which he said for a neurological reaction can be a very long time.
The researchers discovered the actual brain neurotransmitter that activates muscarine receptors -- another chemical, acetylcholine -- sends a signal to these newly discovered brainstem neurons, switching them on for the lengthy minute or so durations.
Alford said the finding opens up new insights into animal locomotion.
"It's a system for turning on your locomotor system and making you walk or run in a very coordinated, straight-line fashion sustaining locomotion for a considerable time," he said. "This simply was not known to exist before we discovered it."
The role of the neurotransmitter acetylcholine may ultimately suggest new Parkinson's disease treatments. While a key Parkinson's symptom is tremor, an advanced stage symptom is the inability to start a movement, such as walking. Symptoms associated with Parkinson's can be helped by reducing acetylcholine-mediated neurotransmission in the brain, but little work has focused on brainstem muscarine receptors in this disease.
"This may be a backdoor finding into a secondary effect of Parkinson's disease that's not well studied because most research emphasis has been on dopamine and the basal ganglia, a different neurotransmitter and region of the brain," Alford said.
Major funding for the research came from the National Institute of Neurological Disorders and Stroke, and the Canadian Institutes of Health Research.
Chicago and Montreal researchers studying the lowly lamprey eel have identified an overlooked nervous system pathway running parallel to known brainstem locomotor command circuitry in vertebrates such as birds, fishes and mammals.
The finding is reported in Nature Neuroscience, online May 16, and highlighted in the magazine's "news and views" section.
Simon Alford, University of Illinois at Chicago professor of biological sciences and the article's corresponding author, said the role of a neurotransmitter associated with this parallel pathway may also suggest new research directions for treating Parkinson's disease.
Alford, along with his former graduate student and lead author Roy Smetana, now a University of Pittsburgh resident in psychiatry, worked with Université de Montréal and Université de Québec à Montréal neurobiologist Réjean Dubuc and his post-doctoral researcher Laurent Juvin in trying to sort out how the neurotransmitter analog muscarine modifies sensory information going to the brain.
Their work determined that muscarine stimulated neural activity, leading to locomotion in the laboratory lampreys.
The group focused its attention on a collection of brainstem neurons that tell the spinal cord to generate motor output that enables walking and other locomotion.
"We started looking at this group of neurons, which in the lamprey are conveniently very large, so they're easy to plant electrodes and record from," said Alford. "We discovered the muscarinic excitation was not working on these cells, but on a previously unknown group of cells within the brainstem."
What's more, these newly discovered brainstem neurons showed what Alford called a "very odd response" to the muscarine.
"Instead of just turning on -- like a synapse turns on a neuron and makes it fire -- when you put muscarine on these cells, they turn on and stay on" for a minute or longer which he said for a neurological reaction can be a very long time.
The researchers discovered the actual brain neurotransmitter that activates muscarine receptors -- another chemical, acetylcholine -- sends a signal to these newly discovered brainstem neurons, switching them on for the lengthy minute or so durations.
Alford said the finding opens up new insights into animal locomotion.
"It's a system for turning on your locomotor system and making you walk or run in a very coordinated, straight-line fashion sustaining locomotion for a considerable time," he said. "This simply was not known to exist before we discovered it."
The role of the neurotransmitter acetylcholine may ultimately suggest new Parkinson's disease treatments. While a key Parkinson's symptom is tremor, an advanced stage symptom is the inability to start a movement, such as walking. Symptoms associated with Parkinson's can be helped by reducing acetylcholine-mediated neurotransmission in the brain, but little work has focused on brainstem muscarine receptors in this disease.
"This may be a backdoor finding into a secondary effect of Parkinson's disease that's not well studied because most research emphasis has been on dopamine and the basal ganglia, a different neurotransmitter and region of the brain," Alford said.
Major funding for the research came from the National Institute of Neurological Disorders and Stroke, and the Canadian Institutes of Health Research.
Wednesday, June 2, 2010
New 'brainstem circuitry' may aid Parkinson's treatment development
Healthcare News
A new brainstem circuitry in mammals may pave the way for an alternative way of looking at Parkinson's disease, according to new research.
Researchers are confident that a new brainstem circuit discovery could help with the treatment of Parkinson's disease in the future.
An overlooked nervous system pathway running parallel to the known brainstem has been discovered in mammals that may offer a new means of treating the condition, according to researchers from the universities of Pittsburgh, Illinois at Chicago, Montreal and Quebec.
The results, which are published in the journal Nature Neuroscience, show how a neurotransmitter associated with this alternative pathway modifies sensory information that is delivered to the brain.
Commenting on the findings, lead author Simon Alford suggested that the research opens up new avenues for general insights into animal and human locomotion.
He explained: "It's a system for turning on your locomotor system and making you walk or run in a very coordinated, straight-line fashion.
"This may be a backdoor finding into a secondary effect of Parkinson's disease that's not well studied because most research emphasis has been on dopamine and the basal ganglia, a different neurotransmitter and region of the brain."
Meanwhile, research published by scientists at the Rush University Medical Center in September suggested that high doses of over the counter vitamin supplements may slow the progression of Parkinson's disease.
A new brainstem circuitry in mammals may pave the way for an alternative way of looking at Parkinson's disease, according to new research.
Researchers are confident that a new brainstem circuit discovery could help with the treatment of Parkinson's disease in the future.
An overlooked nervous system pathway running parallel to the known brainstem has been discovered in mammals that may offer a new means of treating the condition, according to researchers from the universities of Pittsburgh, Illinois at Chicago, Montreal and Quebec.
The results, which are published in the journal Nature Neuroscience, show how a neurotransmitter associated with this alternative pathway modifies sensory information that is delivered to the brain.
Commenting on the findings, lead author Simon Alford suggested that the research opens up new avenues for general insights into animal and human locomotion.
He explained: "It's a system for turning on your locomotor system and making you walk or run in a very coordinated, straight-line fashion.
"This may be a backdoor finding into a secondary effect of Parkinson's disease that's not well studied because most research emphasis has been on dopamine and the basal ganglia, a different neurotransmitter and region of the brain."
Meanwhile, research published by scientists at the Rush University Medical Center in September suggested that high doses of over the counter vitamin supplements may slow the progression of Parkinson's disease.
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