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.