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WEDNESDAY, Nov. 28, 2018 (HealthDay News) – A new study reveals that an experimental gene therapy for Parkinson's disease appears to work by rewiring key areas of the brain.
The researchers focused on 15 patients with Parkinson's disease who, in a previous trial, had received a so-called GAD gene therapy. GAD is an enzyme that stimulates the production of a brain chemical involved in the control of movement.
In the previous trial, patients had improved their movement problems after receiving injections of the GAD gene into the brain.
What was unclear was precisely why, said researcher David Eidelberg, director of the Neuroscience Center at the Feinstein Institute of Medical Research, in Manhasset, New York.
Thus, for the new study, the Eidelberg team examined specialized brain scans in 15 of the patients in the trial. The investigators found an unexpected response: gene therapy did not alter the abnormal brain circuits marking Parkinson's disease.
Instead, he basically rewired a small area of the brain, partially to compensate for faulty circuits.
"He created his own set of circuits," said Eidelberg. "The circuit of the disease continues – so it's not a cure."
Nevertheless, he added, gene therapy seems to be fostering new brain connections that can benefit people with Parkinson's disease.
The results of the study were published online on November 28 in Translational medicine science.
Parkinson's disease affects nearly a million people in the United States alone, according to the Parkinson Foundation.
The root cause is unclear, but as the disease progresses, the brain loses cells that produce dopamine – a chemical that regulates movement. As a result, people suffer from symptoms such as tremors, stiff limbs, balance and coordination problems that become progressively worse over time.
There are treatments to reduce these symptoms, including drugs that increase dopamine levels or mimic the actions of dopamine. Another option for some patients is deep brain stimulation (DBS), where electrodes are implanted in a specific area of the brain to deliver continuous electrical impulses. This is thought to help by removing any abnormal electrical activity.
GAD gene therapy is performed by inserting the gene into an inactivated cold virus. This viral "vector" is infused into a specific area of the brain called the subthalamic nucleus, which is one of the brain regions targeted in the treatment with DBS.
Originally, the researchers added, the researchers thought that gene therapy would work in the same way as DBS.
But based on the new findings, this is not the case.
Dr. Michael Okun is Medical Director of the Parkinson's Foundation. He called the study "fascinating".
"This has shown that GAD gene therapy, unlike SCP of the subthalamic nucleus, has not changed the expected cerebral network of Parkinson's disease," Okun said. "Instead, he opted for adjacent non-motor pathways."
Why is it important? One of the reasons, according to Okun, is that it offers an "important lesson" for the field of gene therapy.
Researchers can not make assumptions about the "mechanism of action" of a therapy, he said, depending on the area of the brain targeted.
Eidelberg added another point: in future studies, researchers could use brain imaging to make sure that patients' symptom improvements are due to a real effect of gene therapy – rather than to the brain. to a "placebo effect".
In the initial trial, which involved a few dozen patients with Parkinson's disease, some patients were randomly assigned to receive GAD gene infusions. The rest underwent a "fictitious" comparison procedure.
Over a six-month period, both groups experienced improvement in movement-related symptoms such as stiffness and tremors. But the gene therapy group has seen bigger gains.
"It was not a slam dunk," said Eidelberg. "But they were better and that persisted until the mark of one year."
With such therapy, there is a theoretical concern that the infused gene will have unexpected effects.
"What we have seen is that this gene remains in place," Eidelberg said. "It does not spread throughout the brain."
In the initial trial, there were no red flags, according to the researchers. The most common side effects were temporary headaches and nausea.
Various research teams are studying different approaches to gene therapy for Parkinson's disease. According to Eidelberg, the hope is to develop additional options that work for at least some patients, possibly releasing them from taking daily medications.
At this point, he noted, there is "a lot of interest" in making a larger, more advanced trial of GAD therapy. But none has yet begun.
This study was funded by Neurologix Inc., the company that developed gene therapy.
More information
The Parkinson Foundation has more information on the treatment of Parkinson's disease.
SOURCES: David Eidelberg, MD, Director, Center for Neuroscience, Feinstein Institute for Medical Research, Manhasset, N.Y .; Michael Okun, MD, Medical Director, Parkinson's Foundation, Miami; November 28, 2018, Translational medicine scienceonline
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