First Gene Therapy Trial In Parkinson's Shows Promising Results

Armen Hareyan's picture

Parkinson's Disease

The world's first-ever gene therapy clinical trial in patients with advanced Parkinson's disease significantly reduced their symptoms.

The trial suggests surgery to deliver a modified gene directly to the brain could be a safe new treatment option for a number of neurodegenerative diseases.

The results suggest gene therapy shows promise as an alternative to medications, which tend to lose effectiveness over time in patients with Parkinson's, and deep brain stimulation surgery, the current best option to reduce movement problems associated with the disease, said Matthew During, professor of molecular virology, immunology and medical genetics at Ohio State University Medical Center and senior author of the study.

The Phase 1 trial results are published in the current issue of the journal The Lancet.

The researchers targeted the same region of the brain that serves as the focal point for deep brain stimulation, delivering the engineered gene directly to the brain's subthalamic nucleus.


"This therapy re-established normal chemistry in the brain and resulted in an overall 25- to 30-percent improvement in the Parkinson's disease rating score, which translates to a major change in quality of life for these patients," During said. "This provides hope for patients who have exhausted every other available medical treatment."

Parkinson's disease is caused by degeneration of nerve cells within the brain that produce the neurotransmitter dopamine. Depletion of this chemical results in impaired control of body movement. Medications may temporarily minimize the symptoms of Parkinson's disease, but cannot halt the degeneration of the selected brain cells.

During and colleagues developed an experimental drug intended to reverse movement problems by re-establishing normal brain activity within motor circuits. They targeted the glutamic acid decarboxylase (GAD) gene because it produces GABA, the major inhibitory neurotransmitter in the brain. The researchers packaged the gene into an adeno-associated virus to enable efficient delivery of the gene into the brain.

The surgery to inject the experimental therapy was performed on 12 patients at New York Presbyterian Hospital. They were screened in the weeks before surgery and one, three, six and 12 months after the surgery for symptoms and evidence of any adverse events. The surgery was performed on only one side of the brain for safety reasons.

Patients were divided into three groups, receiving low, medium or high doses of the gene therapy. All patients experienced substantial improvements in movement control on the side of their bodies opposite the treatment, both with and without the help of oral medications. The dose differences did not affect the therapy's effectiveness, During said.

Ratings continued to improve over the course of a year, and at 12 months, 10 of the 12 patients continued to show improved control over their movement. Five of the patients had total, bilateral improvements ranging from 40 percent to 65 percent despite having only one hemisphere treated. Ratings were based on the Unified Parkinson's Disease Rating Scale, which measures such characteristics as motor ability, mood and ability to perform routine daily activities. Blinded positron emission tomography (PET) scans of the treated area of the patients' brains also showed a reduction in brain activity associated with neurodegeneration that correlated with the motor improvements.

No adverse events associated with the experimental therapy were reported.

"Though this trial was conducted to test the therapy's safety, seeing patients show such marked improvement without a single adverse event leaves us very encouraged," During said.