A gene therapy called NLX-P101 dramatically reduces movement impairment in Parkinson’s patients, according to results of a Phase 2 study published today in the journal Lancet Neurology. The approach introduces a gene into the brain to normalize chemical signaling.

The study is the first successful randomized, double-blind clinical trial of a gene therapy for Parkinson’s or any neurologic disorder, and it represents the culmination of 20 years of research by study co-authors Dr. Michael Kaplitt, vice chairman for research in the Department of Neurological Surgery at Weill Cornell Medical College and a neurosurgeon at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, and Dr. Matthew During, originally at Yale University and now professor of molecular virology, immunology and medical genetics, neuroscience and neurological surgery at the Ohio State University.

“Patients who received NLX-P101 showed a significant reduction in the motor symptoms of Parkinson’s, including tremor, rigidity and difficulty initiating movement,” says Dr. Kaplitt, who pioneered the approach and helped design the clinical trial. “This not only confirms the results of our Phase 1 trial performed at NewYork-Presbyterian/Weill Cornell but also represents a major milestone in the development of gene therapy for a wide range of neurological diseases.”

“This is great news for the 1.5 million Americans living with Parkinson’s disease,” adds Dr. During, who is the co-inventor, with Dr. Kaplitt, of the gene therapy procedure. “Since this is also the first gene therapy study for a neurological disease to achieve success in a rigorous randomized, double-blind design compared with a sham group, this is also a crucial step forward toward finally bringing gene therapy into clinical practice for patients with debilitating brain disorders.”

Although medical therapy is usually effective for most symptoms of Parkinson’s early in the disease, over time many patients become resistant to treatment or develop disabling side effects. An alternative treatment is electrical deep brain stimulation, which requires the implantation of permanent medical devices in the brain.

In the current study, 45 patients with moderate to advanced Parkinson’s disease who were not adequately controlled with current therapies were enrolled in the double-blind trial, with half randomized to receive the gene therapy and the other half to a “sham surgery” - a mock procedure designed to make patients think they could have received the experimental approach.

The results were significant. Half of patients receiving gene therapy achieved dramatic symptom improvements, compared with just 14 percent in the control group. Overall, patients receiving gene therapy had a 23.1 percent improvement in motor score, compared to a 12.7 percent improvement in the control group. This greater improvement in the gene therapy patients compared with the sham patients was statistically significant over the entire six-month blinded study period. (Dr. Kaplitt explains that the improvements in the control group were likely a chimera, the result of placebo effect or a similar phenomenon called regression to the mean.)

“Improved motor control was seen at one month and continued virtually unchanged throughout the six-month study period,” says Dr. Kaplitt, who also serves as associate professor of neurological surgery and director of the Laboratory of Molecular Neurosurgery at Weill Cornell Medical College. “Patients also reported better control of their medication and no worsening of non-motor symptoms.”