Treating Parkinson's disease patients with the experimental drug GM1 ganglioside improved symptoms and slowed their progression during a two and a half-year trial, Thomas Jefferson University researchers report in a new study published online November 28 in the Journal of the Neurological Sciences.
Although the precise mechanisms of action of this drug are still unclear, the drug may protect patients' dopamine-producing neurons from dying and at least partially restore their function, thereby increasing levels of dopamine, the key neurochemical missing in the brain of Parkinson's patients.
The research team, led by senior author Jay S. Schneider, Ph.D., Director of the Parkinson's Disease Research Unit and Professor in the Department of Pathology, Anatomy and Cell Biology and the Department of Neurology at Jefferson, found that administration of GM1 ganglioside, a substance naturally enriched in the brain that may be diminished in Parkinson's disease brains, acted as a "neuroprotective" and a "neurorestorative" agent to improve symptoms and over an extended period of time slow the progression of symptoms.
What's more, once the study participants went off the drug, their disease worsened. The study enrolled 77 subjects and followed them over a 120-week period and also followed 17 subjects who received current standard of care treatment for comparison.
"The drugs currently available for Parkinson's disease are designed to treat symptoms and to improve function, but at this time there is no drug that has been shown unequivocally to slow disease progression," said Dr. Schneider. "Our data suggest that GM1 ganglioside has the potential to have symptomatic and disease-modifying effects on Parkinson's disease. If this is substantiated in a larger clinical study, GM1 could provide significant benefit for Parkinson's disease patients."
Symptoms of the Parkinson's disease, which affects over 1 million people in the United States today and is diagnosed in 60,000 adults every year, include tremors, slowness in movement, difficulty initiating movements, difficulty walking, balance problems and decrease in speech volume and facial expression. The motor symptoms of Parkinson's disease result from the death of dopamine-producing neurons in the substantia nigra, the brain region that dies in Parkinson's disease; the cause of this cell death is unknown.
GM1 ganglioside is a chemical that is normally found in the brain and part of the outer covering of nerve cells. It plays important roles in neuron development and survival and modulates a wide variety of cell activities. GM1 has been found to rescue damaged neurons and increase dopamine levels in pre-clinical studies, and has been suggested to have beneficial effects in other neurodegenerative conditions.
Dr. Schneider and his team made a case for the use of GMI for Parkinson's disease beginning in the 1980s. The pathological processes contributing to the development and progression of Parkinson's disease are still unclear, but they appear to be multifactorial. Because GM1 has effects on many different cellular functions, it seemed a logical approach to try using a drug like GM1 ganglioside to modify the pathological processes occurring in Parkinson's disease, rather than focusing on a specific potential disease mechanism, said Dr. Schneider.
"Instead of a magic bullet, we think of it like a magic shotgun," he said. "This study was truly a success of translational research."
The GM1 research started in mice, where Dr. Schneider and his team found that animals with an experimentally induced form of Parkinson's disease and administered GM1 had significantly higher levels of dopamine in their brains and less loss of dopamine neurons than animals that did not receive GM1.
A follow-up study in a non-human primate Parkinson model found similar results: animals that received GM1 had higher levels of dopamine than animals that did not and had a significant improvement in Parkinson symptoms.
In the late 1990s, Dr. Schneider conducted a short-term study (16 weeks) using GM1 in a small number of patients. Improvement in symptoms was observed in patients who received GM1 compared to patients who received a non-active placebo. However, in order to determine if there was potential for GM1 to slow the progression of the disease, they would have to study patients over a longer period of time-which led them to this current study.