Phase I trial of Gene Therapy to Treat Parkinson's Disease Nears Completion
Apr 24, 2005 - 4:33:38 PM
Neurologix Inc. (OTCBB:NRGX) today announced that on April 20, 2005, its scientific co-founder, Michael G. Kaplitt, M.D. Ph.D., presented a clinical update as the Company sponsored landmark Phase I gene therapy trial for the treatment of Parkinson's disease nears completion. This update was given at the 73rd annual meeting of the American Association of Neurological Surgeons (AANS) held in New Orleans.
Dr. Kaplitt highlighted the rationale for targeting the overactive subthalamic nucleus in Parkinson's disease patients with the GAD (glutamic acid decarboxylase) gene, which synthesizes the major inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA).
He also reported that he completed the surgical gene therapy procedure on a total of 11 patients at The New York Presbyterian Hospital/Weill Medical College of Cornell University. These patients are being monitored and evaluated neurologically before and for one year after surgery by Drs. David Eidelberg and Andrew Feigin at the North Shore Hospital Long Island Jewish Movement Disorder Clinic. The first four patients were treated with the lowest-dose and have now been followed for more than one year. Three of the four patients treated in the second, mid-dose cohort have been followed for more than six months. The remaining four patients, including three in the highest dose cohort, have been followed for intervals up to six months.
The primary outcome measure of this phase I study is safety, and Dr. Kaplitt reported that to date there has been no evidence of any treatment-related adverse effects.
About the Neurologix Phase I Clinical Trial
The Phase I trial, which is the first FDA-approved clinical trial to test gene therapy to treat Parkinson's disease, is an open-label dose-escalation study with four patients in each of three escalating dose cohorts. The third cohort of four patients receives 10 times the dose of the first cohort. The 12 patients participating in the trial must have been diagnosed with severe Parkinson's disease of at least five years duration and who no longer adequately respond to current medical therapies.
The Gene Therapy Procedure
The surgery entails a stereotactic neurosurgical procedure performed under local anesthesia. First, MRI is used to image the target subthalamic nucleus (STN) region of the brain.
The STN is mapped using microelectrodes by recording from single neurons as the electrode is slowly moved towards the STN. Once a signature firing pattern is obtained confirming that the electrode is in the STN, the fine-wire electrode is removed, leaving only the microelectrode sheath through which a hair-thin (170 microns) hollow tube is inserted.
Thirty-five microliters containing 3.5 billion particles of the "AAV" (adeno associated virus) viral vector (and a correspondingly higher dose in subsequent cohorts) containing a GAD gene (cDNA), is then infused at 0.5 microliters/minute, together with 15 microliters of 25% mannitol. After the 100-minute infusion period, the delivery catheter is withdrawn and the incision is closed. No hardware is left behind following this procedure.
"We are pleased and encouraged with our progress to date and look forward to the next phase, which will focus on the efficacy of our proprietary treatment for patients with this disease," said Dr. Michael Sorell, CEO of Neurologix.
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