Jefferson Researchers Provide Leads To Potential Parkinson's Treatment

June 22, 1998

A Natural Substance In The Cell Membrane May Either Protect Or Stimulate Brain Cell Activity

A naturally occurring substance in the cell's membrane may improve symptoms in Parkinson's disease patients and perhaps even help slow down the progression of Parkinson's, according to studies by researchers at Jefferson Medical College of Thomas Jefferson University in Philadelphia.

Jay S. Schneider, Ph.D., professor of pathology, cell biology and anatomy and neurology and his co-workers compared a drug, GM1 ganglioside, with a placebo in 45 patients with Parkinson's disease receiving a 16-week course of treatment.

"At the end of the study, test scores in the Unified Parkinson's Disease Rating Scale, which is a standard scale to measure motor abilities, showed a significant difference between those who received the drug and those who did not," says Dr. Schneider. He and his colleagues at Jefferson report their findings in the June issue of the journal Neurology.

The study was a double-blind trial, with neither the researchers nor the patients knowing who receives the drug. GM1 ganglioside is a normal part of the cell membrane that plays an important role in cell growth, development, signal transduction and repair after injury.

According to Dr. Schneider, many of the patients' symptoms, such as rigidity and slow movement, improved during participation in the trial. Patients also reported that they were able to function better in performing daily living activities, such as dressing and handling eating utensils. "Overall, every patient receiving GM1 improved to some degree," he says. "They had less stiffness, less bradykinesia or slowness of movement, and better manual dexterity and motor coordination."

While some participants in the placebo group also slightly improved, the condition of the majority of those who did not receive the drug remained unchanged.

Dr. Schneider and his group continue to follow 21 patients who wanted to continue taking the drug upon study completion. "Most of these patients have received GM1 treatment now for at least two years," he notes. "The condition of 18 of these 21 patients is better now than it was two years ago when they first began the trial. Although they have improved with the treatment, the improvements in many patients have leveled off."

Dr. Schneider recently presented these findings of the long-term follow-up of these patients at the annual meeting of the American Academy of Neurology.

"Some patients report significant improvements in the quality of their life, though others say improvements have been more modest," he says. "For many patients who have used GM1 for two years or more, it's not so much that they feel that symptoms continue to improve, but they don't feel they are getting substantially worse. For a progressive disease, that's something."

Why? One reason, he explains, could be that the drug somehow stimulates remaining dopamine-producing nerve cells to work better or causes regrowth or sprouting of dopamine nerve endings in the brain. He would like to find out if GM1 is playing either a neuroprotective or neurostimulatory role in patients' improvements.

More than one million people in the United States suffer from Parkinson's disease. It commonly strikes people over 50. Symptoms include hand tremor, slowness in movement, difficulty initiating movements, difficulty walking, shuffling feet, decrease in speech volume, fatigue, and balance problems. In Parkinson's, sufferers lack the brain chemical dopamine due to the death of dopamine-producing nerve cells and their endings.

Dr. Schneider is "proposing to do another double-blind trial, but this time get images of the patients' brains to visualize and count the number of dopamine nerve terminals before the start of the study, and then again after six months, one year, and two years being on therapy." He notes that "by comparing brain images with the clinical status of these patients, we can see if there is any nerve end sprouting or regrowth that can explain clinical improvement. In addition, over time we will be able to see if GM1-treated patients have a slowed loss of dopamine nerve terminals and slowed symptom progression compared to Parkinson's patients, matched for age and disease duration, who don't take GM1." -more- Parkinson disease/page 2

He explains, "We would expect to see a natural decline in dopamine nerve terminal in these patients, and in the GM1 group, we would hope to see either no decline, or a best, a slight increase. This might be fairly definitive evidence of the drug's beneficial effects."

In earlier animal studies, Dr. Schneider and his coworkers found that injecting GM1 ganglioside improved Parkinsonian symptoms, increased levels of dopamine in the brain and stimulated nerve terminal sprouting. "It possibly saved damaged dopamine cells from dying," he notes.

Thomas Jefferson University

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