November 2004

University of South Florida Health Sciences Center

USF neuroscientists awarded $1.1 million NIH grant to improve Alzheimer's vaccine

Tampa, FL (Nov. 10, 2004) -- University of South Florida College of Medicine neuroscientists have been awarded a $1.1 million federal grant to improve the safety and effectiveness of an Alzheimer's vaccine in a mouse model.

"This approach shifts the focus from treating symptoms of Alzheimer's disease to treatments that slow down the disease or prevent it altogether," said Jun Tan, MD, PhD, director of the Neuroimmunology Laboratory in the USF Department of Psychiatry.

Dr. Tan is principal investigator for the four-year grant from the National Institute for Neurological Disorders and Stroke. He will work with co-investigator David Morgan, PhD, director of the Alzheimer's Disease Research Laboratory in the USF Department of Pharmacology and Therapeutics.

The study builds on previous USF laboratory and animal model studies that tracked the role of the brain's immune system in Alzheimer's disease. Under certain circumstances, immune cells in the brain, known as microglia, promote the inflammatory and destructive process that can lead to Alzheimer's disease.

The USF researchers demonstrated that once a specific molecule on the surface of microglia, CD40, gets activated by its partner, CD40 ligand, the scene is set for microglial injury to the main cells in the brain � the neurons. They also showed that the trigger for this harmful immune response associated with brain inflammation can be blocked by an antibody.

In the newly funded study, Dr. Tan and Dr. Morgan plan to administer this anti-CD40 ligand antibody to mice genetically engineered to develop symptoms similar to Alzheimer's disease. The mice also will be immunized with an investigational anti-Alzheimer's vaccine shown to remove beta amyloid plaques that accumulate in the brain, thereby leading to nerve damage and memory loss. While the vaccine has shown clear benefit in mice, some Alzheimer's patients participating in clinical trials of the vaccine fell ill with brain inflammation.

The researchers hypothesize that the combination treatment may have "super-additive effects" in removing Alzheimer's-associated plaques from the brain, while protecting the brain from the side effect of microglia-induced inflammation.






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