NZ Central to Parkinson's Disease Treatment Hopes

New Study Offers Hope For Future Treatment Of Parkinson's Disease

-- First Clinical Trials Using Gene Therapy for Parkinson's Likely to Begin by End of Year --

Auckland, New Zealand and New York, NY: The success of a new gene therapy approach to Parkinson's Disease - developed by University of Auckland scientist Dr Matthew During and co-researchers in Auckland and Weill Cornell Medical College in the United States - is reported today in the prestigious journal Science.

The report describes the potential for this therapy to affect the overall progression of the disease itself. In another significant milestone, the U.S. Food and Drug Administration (FDA) has given its approval to move the therapy into small Phase 1 clinical trials. This will be the first time in the world that gene therapy will be used in the clinic to treat Parkinson's.

"We are using gene therapy to "re-set" a specific group of cells that have become overactive in an affected part of the brain, causing the impaired movement and other symptoms associated with Parkinson's Disease," said Dr During.

"We are very encouraged that in addition to the affect this therapy has on quieting symptoms, we also present evidence that suggests it may arrest or delay disease progression."

People with Parkinson's Disease have a profound loss of a specific group of nerve cells deep in the brain which make dopamine, a signaling molecule. The loss of dopamine leads to a disturbance in the brain's network activity controlling movement. In the centre of this network is a region called the subthalamic nucleus (STN), which in Parkinson's Disease is extremely overactive, and if silenced leads to a dramatic reduction in the symptoms.

Targeting the overactive cells, Dr During and his co-researchers have developed a model that enables the "GAD" gene to be efficiently delivered into the affected region of the brain.

GAD is responsible for making a small molecule called GABA, which is released by nerve cells to inhibit, or dampen activity. After this gene therapy is introduced, the overactive cells are "re-set" and brain network activity controlling movement returns towards more normal function.

Although medical therapy is usually effective for most symptoms of Parkinson's, over time many patients become resistant to treatment or develop disabling side effects.

"Current surgical therapies for Parkinson's attempt to interrupt this network abnormality by destroying overactive brain areas or placing DBS (deep brain stimulation) electrodes to quiet these areas. Both of these treatments, however, have certain limitations and side effects," said Dr. During.

"Our approach is based on a similar rationale, but we use gene therapy to adjust the chemical signaling of these brain areas to a more normal setting. This exploits the best parts of current therapy but makes it more powerful, less invasive and potentially safer."

The Science paper reports on testing of this theory using a combination of techniques to measure brain function. Five tests were conducted. These tests showed the GAD gene was present and producing GABA as anticipated. Furthermore, the researchers were able to show the positive effects of the therapy were retained and no further signs of Parkinson's developed. Preliminary results show the therapy is safe and there are no toxicities associated with the treatment.

Small-scale Phase I trials of this therapy are anticipated to begin within the next few months. Selected patients will undergo surgical gene therapy at New York Presbyterian Hospital/Weill Medical College of Cornell University by neurosurgeon and co-principal investigator, Dr Michael G. Kaplitt. These patients will be recruited and followed by Drs David Eidelberg and Andrew Feigin at the North Shore Hospital Long Island Jewish Movement Disorder Clinic. The initial trial will be limited to 12 patients with severe Parkinson's Disease, of at least five years duration, for whom current therapies are no longer effective.

"The Science report and our team's translation of this approach to treatment of human disease represent the culmination of over a decade of research in this area," said Dr During, who is the FDA sponsor and chief scientific investigator for the clinical trial. "Our primary objective has been to stress patient safety above all else, and the NIH (U.S. National Institutes of Health) and FDA have helped us design a clinical intervention which has exciting efficacy potential and attempts to minimize in any way possible risks of adverse events to patients in the study. It is our hope that with this approach, our trial will help demonstrate that gene therapy in the brain can be both safe and effective."

The Science publication is authored by lead investigator, Dr Matthew J. During, Professor of Molecular Medicine at the University of Auckland, lead author Dr Jia Luo, and co-investigator Dr Michael G. Kaplitt, Director of Stereotactic and Functional Neurosurgery and Professor at Weill Cornell Medical College. Dr During and Dr Kaplitt are also co-principle investigators on the upcoming clinical trial of this therapy.

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