Novel Nasal Vaccine is Effective in Treating Mouse Model Alzheimer's Disease

Treating Alzheimer's Disease

Continuing a long-standing history in Alzheimer's disease-related study, researchers at Brigham and Women's Hospital (BWH) in an effort to better understand and treat the disease, have identified a novel new vaccine that has been shown to slow disease development in mouse models. According to the researchers, the next step is to bring this vaccine, which contains compounds known to be safe for humans, to clinical trial. Details of this research will be published on-line August 11, 2005 and will appear in the September 2005 print issue of The Journal of Clinical Investigation.

Alzheimer's disease is the most common form of senile dementia, affecting more than 18 million people worldwide. As the baby-boom generation ages, this number is expected to rise. To date, researchers have amassed evidence that the disease is caused by abnormal accumulation of a substance in the brain called beta-amyloid. This accumulation interferes with brain function and effects memory and cognition. A major goal in Alzheimer's research is to develop ways to remove this beta-amyloid build-up. One of the strategies for accomplishing this is to trigger the body's own immune system to clear the amyloid from the brain. Previous and current studies have focused on injectable vaccines to induce antibodies to clear the a-beta or direct intravenous administration of anti-a-beta antibody. These earlier trials of injectable a-beta were discontinued because of complications that led to encephalitis.

According to Howard L. Weiner, MD, a neurologist who is co-director of the Center for Neurologic Diseases at BWH and who headed the research team, "This basic science finding has tangible bedside implications. We hope to see this vaccine strategy studied in humans as quickly as possible to help determine if it can slow the progression of Alzheimer's disease. Until we have a cure or a way of preventing the disease, novel new strategies like this are critical to the development of a treatment regimen that will preserve quality of life for those who suffer from the disease."

Previous research found that a vaccine containing a-beta, while promising in mouse models in reducing a-beta, caused encephalitis. The new approach " which was identified as researchers were trying to understand why the encephalitis occurred " is believed to eliminate dangerous side-effects by combining two components, Protollin and glatiramer acetate, both of which have proved to be well tolerated in humans. Protollin is a nasal adjuvant developed by ID Biomedical Corporation based on their Proteosomes technology that has been safely given to humans. Glatiramer acetate (Copaxone ) is an FDA approved drug for the treatment of relapsing forms of multiple sclerosis (MS) manufactured by Teva, Neuroscience.

Weiner, along with lead author Dan Frenkel, PhD and Ruth Maron, PhD, both of the BWH, and David Burt of ID Biomedical Corporation of Quebec studied transgenic mice with plaques similar to those in human Alzheimer's disease. The animals were injected with the new vaccine with researchers subsequently finding a 73 percent reduction in total a-beta levels. By combining the two known substances, researchers found that cells in the brain that clear the a-beta were activated without toxic side effects. Researchers indicate this process occurs through the stimulation of microglial cells, which "eat" the a-beta.

"This vaccine is a novel approach to treating this disease," said Weiner who is also director of the Partners MS program. The vaccine was discovered in his laboratory in which research principles related to multiple sclerosis were applied to the Alzheimer's disease model. "It stimulates the body to attack the a-beta, without stimulating antibody against a-beta thus eliminating risky side effects associated with anti-a-beta immune responses."

According to Weiner, the next steps are to refine our understanding of how this vaccine works in animal models. However, he indicates that enough is now known to initiate human clinical trials. Weiner hopes, pending FDA approval, to initiate phase I trials in humans in 2006 under the direction of Reisa Sperling, MD, head of the Center for Alzheimer's Research and Treatment at BWH.

This research was supported by the National Institutes of Health and a Human Frontier Science Program Fellowship.