A team led by physician-scientists at New York-Presbyterian Hospital/Weill Cornell Medical Center has successfully completed the first-ever phase I clinical trial using gene therapy to reduce the symptoms of Parkinson’s disease.
Patients with Parkinson’s have a reduced neurotransmitter called GABA. GABA is a major inhibitory neurotransmitter in the brain that helps quiet excessive neuronal firing. The researchers’ bold idea was to insert the GABA-producing gene glutamic acid decarboxylase (GAD) back into an area of the brain called the subthalamic nucleus, a key regulatory center within this motor circuit.
"Our hope was that with a single operation to this single site, we could boost GABA production and thereby normalize the function of the entire circuit," said lead researcher Dr. Michael Kaplitt, associate professor of neurological surgery and the Victor and Tara Menezes Clinical Scholar in Neurological Surgery at Weill Cornell Medical College, and director of Movement Disorders Surgery at New York-Presbyterian Hospital/Weill Cornell Medical Center. "Not only would this alter the chemical balance in the subthalamic nucleus; it should also provide GABA to other parts of the network that weren't getting enough of the neurotransmitter."
Twelve patients, 11 male and 1 female, participated in the study and were followed for 1 year. Although all the patients were symptomatic on both sides of their brains, only one side was treated, thus providing an untreated side for comparison. The Unified Parkinson’s Disease Rating Scale (UPDRS) was used to measure motor function, and positron emission topography (PET) scans were used to track changes in brain activity. Remarkable improvements were noted in both areas of assessment with no adverse events—no immunological changes or infections, no imaging evidence of toxicity. Further, larger studies are planned.
"We believe that this breakthrough trial has implications that go far beyond Parkinson's research," Dr. Kaplitt says. "It's taken us nearly two decades of hard work to get here, but the success of this trial lays the foundation for the use of gene therapy against neurological diseases generally. We've now shown that the genetic modification of the patient's own brain cells can be done safely, and it appears to have enough effectiveness in this case to justify further exploration — potentially opening up gene therapy for a host of brain disorders."
Illustration: Sir William Richard Gowers, neurologist, researcher and artist, drew this illustration in 1886 as part of his documentation of Parkinson's Disease. The image appeared in his book, A Manual of Diseases of the Nervous System, still used today by medical professionals as a primary reference for this disease. –Wikipedia.
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