Patient Receives First-Ever Gene Therapy for Parkinson's at …

Patient Receives First-Ever Gene Therapy for Parkinson's at NewYork-Presbyterian Hospital/Weill Cornell Medical Center Historic Procedure Also Marks First In Vivo Gene Therapy in Adult Brain

NEW YORK (Aug 20, 2003)

Surgeons at NewYork-Presbyterian/Weill Cornell performed the world's first gene therapy for Parkinson's disease on a 55-year-old New York man on Monday, August 18. The historic surgery, which also marked the first-ever in vivo gene therapy in the brain for an adult neurological disease, was part of a Phase I clinical trial approved by the Food and Drug Administration in October 2002.

The five-hour procedure was performed by Dr. Michael G. Kaplitt, Director of Stereotactic and Functional Neurosurgery at NewYork-Presbyterian Hospital and Assistant Professor of Neurological Surgery at Weill Cornell Medical College. The patient is recovering normally and is expected to return home today, just two days after the surgery was performed.

"Monday's surgery represents the realization of nearly 15 years of research in this area," said Dr. Kaplitt. "The goal of our gene therapy approach is to 're-set' a specific group of cells that have become overactive in an affected part of the brain, causing the impaired movements associated with Parkinson's disease. We hope that this trial, which is the first of its kind, will prove to be a safe treatment to allow gene therapy to move forward for Parkinson's disease and other brain disorders."

Dr. Antonio M. Gotto, Jr., Dean of Weill Cornell Medical College, said: "This research represents a new approach to treating one of the most devastating diseases known to man."

Dr. Herbert Pardes, President and CEO of NewYork-Presbyterian Hospital, said, "This major breakthrough can only be realized in an academic medical center, such as ours, where a unique synergy between bench and bedside, between research and patient care, can meet and flourish."

In the procedure, Dr. Kaplitt pinpoints the optimal location in the patient's brain using information from an advanced 3T MRI image, which is subsequently merged with a CT scan, using the latest computer imaging technology. Then, the final target is confirmed using fine electrical probes that identify the signature pattern of electrical activity of individual cells within the brain. During this process, the patient is awake and not medicated because medication and anesthesia can confuse the electrical information obtained. With the target obtained, the gene therapy agent (adeno-associated virus or AAV) is slowly delivered through a very fine catheter. After a 90-minute infusion, the catheter is removed, the skin closed, and the patient sent to the recovery room.

AAV is the means by which the GAD (glutamic acid decarboxylase) gene enters the appropriate brain cells and begins production of a protein that produces GABAa molecule that is released by nerve cells to inhibit, or dampen, activity. "Our intent, ultimately, is to normalize the chemical signaling of key affected brain areas in order to reduce the devastating effects of Parkinson's," says Dr. Kaplitt.

In 1994, Dr. Kaplitt was the lead author of a paper published in Nature Genetics, along with senior author Dr. Matthew During, Professor of Molecular Medicine at the University of Auckland, which demonstrated, for the first time, that AAV could be a safe and effective vehicle for gene therapy in the brain. Last October, Dr. During was the lead author and Dr. Kaplitt the co-author of a paper in Science demonstrating the feasibility of the gene therapy approach used in today's operation. Since 1994, AAV has been used safely in several clinical gene therapy trials, and the virus has never been associated with any human disease.

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Patient Receives First-Ever Gene Therapy for Parkinson's at ...