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Vaccine Reduces Parkinson's Disease Neurodegeneration in Mice


For release: Wednesday, July 28, 2004

For the first time, researchers have shown that an experimental vaccine can reduce the amount of neurodegeneration in a mouse model for Parkinson's disease. The finding suggests that a similar therapy might eventually be able to slow the devastating course of Parkinson's disease in humans.

The experimental treatment in this study is among the first to show potential for slowing brain degeneration in this disease, the researchers say. Currently available therapies can treat symptoms of the disease, but they do not prevent the loss of brain cells.

"This is a novel therapeutic approach to stop the damaging inflammation associated with neurodegeneration. It is exciting because an approach like this may be beneficial in a variety of neurodegenerative diseases in addition to Parkinson's disease," says Diane Murphy, Ph.D., a National Institute of Neurological Disorders and Stroke (NINDS) program director for Parkinson's disease research. The research was funded in part by the NINDS and appears in the June 22, 2004 issue of the Proceedings of the National Academy of Sciences (PNAS). 1

Studies in the last decade have shown that inflammation is common to a variety of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, HIV-1 associated dementia, and amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). The inflammation in these diseases involves activation of microglia - specialized support cells in the brain that produce immune system signaling chemicals called cytokines. Although inflammation can be damaging, Michel Schwartz, Ph.D. and colleagues at the Weizmann Institute in Rehovot, Israel, have pioneered research which shows that activating immune cells in specific ways also may lead to neuroprotective responses in animal models of spinal cord and brain injury.

In the new study, Howard E. Gendelman, M.D., of the University of Nebraska Medical Center in Omaha, along with graduate student Eric Benner and colleagues, experimented with a drug called copolymer-1 (Copaxone). Previous studies have shown that Copaxone, which is commonly used to treat multiple sclerosis, increases the number of immune T cells that secrete anti-inflammatory cytokines and growth factors. The researchers took immune cells from mice that had received Copaxone immunization and injected them into mice which had received injections of a drug called MPTP. MPTP leads to Parkinson's-like neuronal degeneration in the brain.

Mice which received the Copaxone-treated immune cells had significantly less degeneration of dopamine-producing neurons in their brain than mice which did not receive the treated cells. These mice also lost fewer dopamine-transmitting nerve fibers than control mice and had only a small decrease in the amount of dopamine produced in the brain. Dopamine is a nerve signaling chemical (neurotransmitter) that controls movement; a loss of dopamine-producing neurons is the central problem in Parkinson's disease.

The researchers found that T cells in the treated mice migrated to the damaged area of the brain, reduced the harmful reactions of the microglia, and triggered a neuroprotective response. In addition, the vaccine dramatically increased the amount of a growth factor called GDNF (glial-derived neurotrophic factor) that helps prevent neurodegeneration.

"This study provides a proof of concept," says study coauthor Serge Przedborski, M.D., Ph.D., of Columbia University in New York. The vaccination modifies the behavior of the glial cells so that their responses are beneficial to the nervous system rather than harmful, he explains.

The researchers injected Copaxone-treated cells in this study because MPTP destroys the mouse immune system, Dr. Gendelman says. The MPTP mice needed replacement immune cells in order to respond to the drug. However, Copaxone could be given to humans directly, he says.

The researchers are now planning follow-up studies to confirm their results and to identify the specific cytokines, nerve growth factors, and other proteins that play a role in the protective response. Other work is needed to determine how to translate the study results into a therapy for humans and to make sure the treatment is safe for patients with Parkinson's, who may not react to the drug in the same way that MS patients do, Dr. Przedborski says.

While Copaxone is currently approved by the U.S. Food and Drug Administration for use in treating multiple sclerosis, the dose needed to treat Parkinson's will probably be quite different from the dose used in treating MS, says Benner. The timing of treatment may also prove critical. Therefore it is premature for patients with Parkinson's disease to begin taking the drug. Currently available doses of the drug could be ineffective or even harmful for these patients, he adds.

The NINDS is a component of the National Institutes of Health within the Department of Health and Human Services and is the nation's primary supporter of biomedical research on the brain and nervous system.

Reference: 1 Benner EJ, Mosley RL, Destache CJ, Lewis TB, Jackson-Lewis V, Gorantia S, Nemacheck C, Green SR, Przedborski S, Gendelman HE. "Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease." Proceedings of the National Academy of Sciences, June 22, 2004, Vol. 101, no. 25, pp. 9435-9440.

- By Natalie Frazin



 

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Last Modified November 21, 2014