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2016 Grants - Castle
AAV Vectors for Widespread and Specific BDNF Delivery to the Cortex in Alzheimer’s Disease
Michael J. Castle, Ph.D.
University of California, San Diego
La Jolla, California
2016 Alzheimer’s Association Research Fellowship (AARF)
Can a novel method of delivering growth factors to the brain help promote nerve cell survival in Alzheimer’s disease?
BDNF (brain-derived neurotrophic factor) is a small protein that occurs naturally in the brain and is essential for the health and survival of certain types of nerve cells. Recent studies suggest that BDNF may help prevent nerve cell loss and preserve learning and memory in Alzheimer’s-like mice and non-human primates. While BDNF holds promise for the treatment of Alzheimer’s disease in humans, it has been challenging to develop drug-based therapies because the BDNF molecule cannot cross the blood-brain barrier, a protective structure that surrounds the brain and controls what types of molecules can enter.
To address these problems, scientists have developed adeno-associated viral (AAV) vectors which are modified viruses that can safely deliver a gene to make BDNF into the brain. A current limitation is that AAV-BDNF must be injected into many areas of the brain over an extended period of time which is not feasible for human studies.
Michael J. Castle, Ph.D., and colleagues have developed a novel method for delivering AAV-BDNF into the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord. Using this technique, AAV-BDNF can be delivered to a large area of the brain from a single injection. In addition, Dr. Castle’s team has modified the virus to contain controller genes, which will only allow BDNF production in nerve cells of the cerebral cortex. The cerebral cortex is the outermost layer of the brain and controls many of the memory and reasoning functions that are affected by Alzheimer’s disease. The researchers will determine if their novel method for BNDF delivery can prevent the death of nerve cells and preserve brain function in Alzheimer’s-like mice.
If successful, the results of these studies could provide the foundation for the development and testing of this novel treatment as a way to protect nerve cells from damage and improve brain function in people with Alzheimer’s disease.