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2012 Grants - Gil-Bea
Pharmacological Manipulation of BDNF as Therapeutic Challenge for Alzheimer's Disease
Francisco J. Gil-Bea, Ph.D.
Foundation for Applied Medical Research
2012 New Investigator Research Grant
In recent years, much Alzheimer's disease research has focused on developing drug therapies that target the disease's biomarkers, including the protein fragment beta-amyloid. Many of these treatments, however, have not yet achieved satisfactory results in clinical trials. In response, some investigators have been exploring other therapeutic strategies for Alzheimer's. Such approaches often focus on helping moderate cognitive decline in people who already have the disease.
Francisco J. Gil-Bea, Ph.D., and colleagues have been studying the therapeutic potential of brain-derived neurotrophic factor (BDNF). This protein occurs naturally in the brain, and it has been shown to prevent nerve cell death, promote the growth of new neurons, and facilitate the development of synapses (the tiny channels through which brain cells send and receive chemical messages). Thus BDNF is important for maintaining proper cell-to-cell communication in the brain and in maintaining cognitive health. Not surprisingly, people with Alzheimer's disease possess reduced levels of this protein. Yet BDNF-related therapies have proven unsuccessful. Because the protein is too large to cross the blood-brain barrier, which protects the brain from foreign substances in the blood, it cannot be delivered to the brain easily. Moreover, treatments that involve large doses of BDNF have caused harmful side effects in animals. In an attempt to develop a safer and more practical BDNF treatment, Dr. Gil-bea and colleagues have found that by boosting the activity of a brain protein called tissue-plasminogen activator (tPA), they could increase BDNF levels in cultured cells. This treatment also made the cells less vulnerable to the toxicity of beta-amyloid and other Alzheimer's-related molecules.
For their current project, the researchers plan to test their tPA/BDNF treatment in mice engineered to develop Alzheimer's-like symptoms. They also plan to identify other mechanisms that may promote BDNF levels in cells and living animals. The results of this work could lead to novel methods for helping people with Alzheimer's cope with their disease.