Significant vaccine advance for Parkinson’s disease therapy

Scientists at the University of Nebraska Medical Center in Omaha and Columbia University Medical Center in New York have discovered a new vaccine approach that successfully prevents the death of brain cells in a mouse model of Parkinson’s disease.

“It’s a significant conceptual advance for Parkinson’s disease therapy,” said Howard Gendelman, M.D., David T. Purtilo Distinguished Chair of Pathology and Microbiology at UNMC and director of the Center for Neurovirology and Neurodegenerative Disorders where the research was conducted. “As of today drugs are available which only treat symptoms of disease. Regrettably, nothing is now available that prevents or reverses the course of brain degeneration. Our vaccine approach changes this by bringing a new excitement to a developing field of investigation called neuroprotective medicine. A vaccine therapy that protects the dopamine nerve cells damaged in Parkinson’s disease is novel.”

“The research is very exciting,” said Serge Przedborski, M.D., Ph.D., professor of neurology and pathology in the Center for Neurobiology and Behavior at Columbia University and a world-renowned expert in Parkinson's disease research. “Using this approach, the harmful aspects of inflammation associated with Parkinson’s disease could be eliminated.”

The discovery, however, is just the beginning, Dr. Gendelman said. More research is being done at UNMC to improve this approach. Some aspects include finding the types of immune cells responsible for the protection, as well as developing diagnostic techniques like enhanced magnetic resonance imaging to track disease progression. Clinical trials in humans are being developed at Columbia University.

“This will change how we treat neurodegenerative diseases,” said Harris Gelbard, M.D., Ph.D., professor of neurology at the University of Rochester Medical Center.

“It’s a groundbreaking advance.”

The CNND has based much of its research on the premise that activation of two types of support cells in the brain – microglia and astrocytes – mediate inflammatory events that contribute to the death of neurons, the nerve cells in the nervous system that receive and send out electrical signals. The destruction of neurons is well known to lead to the development of neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and HIV-1-associated dementia. The vaccine approach can affect the inflammatory brain response and at the same time increase the local expression of neurotrophins or nerve cell growth promoting factors in the brain.

“What we have done is take an evil process (inflammation) and turned it on its heels,” Dr. Gendelman said. “We’ve taken a destructive process and contained it.”

Drs. Gendelman and Przedborski emphasized that although the vaccine protects mice against the type of cell death observed in Parkinson’s disease, there is no guarantee it will act the same way in humans. Clinical trials ultimately will determine if the observations seen in mice can be translated and prove useful in humans with disease.

In mice, however, the concept has shown great promise, preventing the progression of the disease. In their research, CNND scientists injected a brain protein into mice with an experimental form of Parkinson’s disease. “The mice mounted an immune response to the brain protein that turned off inflammation,” Dr. Gendelman said.

The immune cells can go into brain regions that are affected during disease and reduce the inflammation in the area of injury, as it would elsewhere in the body following local infections and trauma. This may be a way to use the body’s own defense to work towards its own repair, Dr. Gendelman said.

Importantly such protective strategies eliminate the need to use more controversial approaches for brain repair including the use of embryonic stem cells and fetal cells, he said. Unlike fetal or stem cells, this vaccine therapy relies on harnessing the body’s own immune system. “It’s a very novel means for combating neurological diseases,” Dr. Gendelman said.

Parkinson’s disease is a chronic, debilitating disease without a cure. There also is no preventive or restorative treatment available. In the United States, at least 500,000 people are believed to suffer from Parkinson's disease, and about 50,000 new cases are reported annually. The incidence is expected to increase as the average age of the population increases. The disorder appears to be slightly more common in men than women.

The vaccine approach utilizes a compound called Copaxone or Cop-1, a Food and Drug Administration-approved and well-tolerated drug. Cop-1 has been used effectively in patients with chronic neuroinflammatory disease such as relapsing remitting multiple sclerosis for more than a decade. Given the safety record for Cop-1 and that current treatments for Parkinson’s disease remain palliative, such a vaccination strategy represents a promising therapeutic avenue that can readily be used in human clinical trials, said Drs. Gendelman and Przedborski.

The findings appear June 14 in the Proceedings of the National Academy of Sciences of the United States of America. PNAS is among the world’s most-cited multidisciplinary scientific journals. The report, titled “Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson’s disease,” appears online June 14. A print copy will be released June 22.

The work was supported in part, by the National Institutes of Neurological Disorders and Stroke, the U.S. Department of Defense, the Alan and Marcia Baer Foundation, the FVB Foundation, Inc., the Lowenstein Foundation, the Lillian Goldman Charitable Trust, the Parkinson’s Disease Foundation and the MDA/Wings-Over-Wall Street.

UNMC is the only public health science center in the state. Its educational programs are responsible for training more health professionals practicing in Nebraska than any other institution. Through its commitment to education, research, patient care and outreach, UNMC has established itself as one of the country's leading centers in cancer, transplantation biology, bioterrorism preparedness, neurodegenerative diseases, cardiovascular diseases, genetics, biomedical technology and arthritis. UNMC’s research funding from external sources now exceeds $65 million annually.

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