[imark3000]

http://www.virtualmedicalcentre.com/...-disease/16112
A ray of hope but what is NLX-P101 ?
Imad

"A gene therapy called NLX-P101 dramatically reduces movement impairment in Parkinson's patients, according to results of a Phase 2 study published in the journal Lancet Neurology. The approach introduces a gene into the brain to normalise chemical signalling.

The study is the first successful randomised, double-blind clinical trial of a gene therapy for Parkinson's or any neurologic disorder, and it represents the culmination of 20 years of research by study co-authors Dr Michael Kaplitt, vice chairman for research in the Department of Neurological Surgery at Weill Cornell Medical College and a neurosurgeon at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, and Dr Matthew During, originally at Yale University and now professor of molecular virology, immunology and medical genetics, neuroscience and neurological surgery at the Ohio State University.

"

[girija]

For more information, visit www.nyp.org and weill.cornell.edu.
Powered by Big Medium™
Contact Info
Andrew Klein
ank2017@med.cornell.edu

How NLX-P101 Gene Therapy Works

Gene therapy is the use of a gene to change the function of cells or organs to improve or prevent disease. To transfer genes into cells, an inert virus is used to deliver the gene into a target cell. In this case, the glutamic acid decarboxylase (GAD) gene was used because GAD makes a chemical called GABA, a major inhibitory neurotransmitter in the brain that helps "quiet" excessive neuronal firing related to Parkinson's disease.

"In Parkinson's disease, not only do patients lose many dopamine-producing brain cells, but they also develop substantial reductions in the activity and amount of GABA in their brains. This causes a dysfunction in brain circuitry responsible for coordinating movement," explains Dr. During.

In the Phase 2 study, each patient in the experimental group received an infusion of the genetic material directly into their subthalamic nucleus, a key brain region involved in motor function. The GAD gene instructed cells in that area to begin making GABA neurotransmitters in order to re-establish the normal chemical balance which becomes dysfunctional within circuits that control movement.

While patients in the Phase 1 study only received the therapy on one side of their brain, patients in the Phase 2 were infused on both sides. And while the infusion happened entirely in the operating room in the previous phase, the current study made use of a novel delivery system conceived by Drs. Kaplitt and During that allowed for the infusion to take place outside of the OR — at the hospital bedside — something Dr. Kaplitt says makes for a more comfortable patient experience.

Drs. Kaplitt and During also designed the sham surgery, one of the most complex of its kind. The challenge was especially great because patients were required to remain awake to enable surgeons to locate the targeted brain area. In the sham procedure, a small indentation was drilled partway into their skull. Pre-recorded audio of a subthalamic nucleus mapping procedure was played while patients were asked to move various body parts, leading them to believe that an actual brain procedure was being performed. Lastly patients were attached to an infusion system that appeared identical to the system used in the gene therapy group but were subcutaneously injected with saline solution instead of the gene therapy.

The NLX-P101 gene therapy was pioneered by Neurologix Inc. scientific founders Drs. Kaplitt and During. The two researchers have been at the forefront of gene therapy research since 1989. They were the first to demonstrate that the viral vector AAV could be an effective gene therapy agent in the brain, which they reported in a 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 in the journal Science in 2002. The Phase 1 clinical trial, performed at NewYork-Presbyterian/Weill Cornell, was the first ever clinical gene therapy trial for Parkinson's or any other adult neurological disorder. 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.

The Phase 2 study was funded by Neurologix Inc., of Fort Lee, N.J., which is developing the adeno-associated virus-borne GAD (AAV-GAD) agent and has licensed intellectual property rights to NLX-P101 gene therapy. Drs. Kaplitt and During are co-founders of the company and remain paid consultants. Additionally, Dr. Kaplitt's father, Dr. Martin Kaplitt, is chairman of the board of Neurologix, and as such has stock ownership and receives salary.
Leading the study were neurologists Dr. Andrew Feigin of the North Shore — LIJ Health System in Manhasset, N.Y., and Dr. Peter A. LeWitt of the Henry Ford Health System in West Bloomfield, Mich.

Additional co-authors include Jason M. Schwalb from the Henry Ford Health System, West Bloomfield Charter Township, Mich; Ali R. Rezai, Sandra K. Kostyk, Karen Thomas and Atom Sarkar from the Ohio State University College of Medicine, Columbus, Ohio; Maureen A. Leehey and Steven G. Ojemann from the University of Colorado School of Medicine, Aurora, Colo.; Alice W. Flaherty and Emad N. Eskandar from the Massachusetts General Hospital, Boston; Mustafa S. Siddiqui and Stephen B. Tatter from the Wake Forest University School of Medicine, Winston-Salem, N.C.; Kathleen L. Poston and Jaimie M. Henderson from the Stanford University School of Medicine, Stanford, Calif.; Roger M. Kurlan and Irene H. Richard from the University of Rochester School of Medicine, Rochester, N.Y.; Lori Van Meter from PharmaNet Development Group, Princeton, N.J.; and Christine V. Sapan from Neurologix Inc., Fort Lee, N.J.

For more information, patients may call (866) NYP-NEWS.
NewYork-Presby

[johnt]

Would a normal drug treatment to increase GABA levels in the brain (e.g. theanine) be effective too?

John

[soccertese]

Originally Posted by johnt

Would a normal drug treatment to increase GABA levels in the brain (e.g. theanine) be effective too?

John

theanine seemed to interfere with my sinemet. but you can easily test it.

[imark3000]

If Theanin increases Gaba, it would be by far better than drilling in the brain and injecting “neutralized” viruses carrying genes. Why on earth that Theanin is not researchedd enough to produce a possible medicine? /Imad

" Able to cross the blood-brain barrier, theanine has psychoactive properties.[5] Theanine has been shown to reduce mental and physical stress,[6] and improves cognition and mood in a synergistic manner with caffeine.[7]

While structurally related to the excitatory neurotransmitter glutamate, theanine only has weak affinity for the glutamate receptor on postsynaptic cells.[8] Rather, its primary effect seems to increase the overall level of the brain inhibitory transmitter GABA. Theanine also increases brain dopamine levels and has a low affinity for AMPA, kainate and NMDA receptors.[9] Its effect on serotonin is still a matter of debate in the scientific community, with studies showing increases and decreases in brain serotonin levels using similar experimental protocols.[10][11] It has also been found that injecting spontaneously hypertensive mice with theanine significantly lowered levels of 5-hydroxyindoles in the brain.[12] Researchers also speculate it may inhibit glutamic acid excitotoxicity.[9] Theanine also promotes alpha wave production in the brain.[5]

Studies on test rats have shown even repeated, extremely high doses of theanine cause little to no harmful psychological or physical effects.[13] Theanine showed neuroprotective effects in one rat study.[14]

A placebo-controlled trial has shown adding theanine to ongoing antipsychotic medication is helpful in reducing some symptoms of schizophrenia.[15]

Several beverage manufacturers are selling drinks containing theanine and are marketing them as drinks to help people focus and concentrate,[16] while other manufacturers claim relaxing and tranquillizing properties.[15]

[edit] Immune system benefitsL-Theanine may help the body's immune response to infection by boosting the disease-fighting capacity of gamma delta T cells. The study, published in 2003 by the Brigham and Women's Hospital, included a four-week trial with 11 coffee drinkers and 10 tea drinkers, who consumed 600 milliliters of coffee or black tea daily. Blood sample analysis found the production of antibacterial proteins was up to five times higher in the tea drinkers, an indicator of a stronger immune response.[17]

[dopadoc]

Nice summary

[Conductor71]

Originally Posted by imark3000

If Theanin increases Gaba, it would be by far better than drilling in the brain and injecting “neutralized” viruses carrying genes. Why on earth that Theanin is not researchedd enough to produce a possible medicine? /Imad

That is a good question, but I think the whole point with Neurologix is to offer a viable alternative to DBS. We are so sold on DBS; we forget that not everyone benefits from it. Both treatments have the goal of reducing number of pills we have to take. Plus, I read where they have a new bedside delivery "innovation"- not sure what it entails but it is far more comfortable than sitting with your head in a cage for 8 hours or enduring a drill in the skull. Waiting 6-8 weeks for brain swelling to go away, only to be tweaked and fine tuned for another 6 months to reach an optimal setting...the potential benefit of GAD therapy over DBS are tremendous especially if you know people who have less than an optimal outcome from DBS.

While patients in the Phase 1 study only received the therapy on one side of their brain, patients in the Phase 2 were infused on both sides. And while the infusion happened entirely in the operating room in the previous phase, the current study made use of a novel delivery system conceived by Drs. Kaplitt and During that allowed for the infusion to take place outside of the OR — at the hospital bedside — something Dr. Kaplitt says makes for a more comfortable patient experience.