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Alzheimer's Disease Research
Completed Award

Photo Pending

Frank LaFerla, Ph.D.

University of California, Irvine
Irvine, CA

Title: BDNF-mediated treatment for neurodegenerative disease
Non-Technical Title: Stem cells as a treatment option for Alzheimer's disease

Acknowledgements: This grant is made possible by a generous bequest from the Stanley B. Gordon & Nicole B Gordon Revocable Survivor’s Trust.
Duration: April 1, 2010 - March 31, 2013
Award Type: Standard
Award Amount: $400,000

Summary:

We will explore the therapeutic benefit of using neurotrophins to treat the cognitive decline that characterizes Alzheimer’s disease. We have generated a significant body of preliminary data that show that animal neural stem cells improve function in two mouse models of Alzheimer’s disease, including one with extensive neurodegeneration. The outcome of the proposed studies will test whether neurotrophins, a factor naturally secreted by neural stem cells, can replicate the effects produced by stem cell transplantation. If this is the case, neurotrophin supplementation would provide a very promising pharmacological approach to Alzheimer’s disease that avoids any untoward effects associated with “cell-based therapies”, including stem cell transplants.

Details:

Alzheimer’s disease (AD) is the most common cause of age-related dementia, yet an effective and long-lasting treatment still does not exist. Recent studies indicate that transplanting neural stem cells can improve brain dysfunction in certain neurological disorders, but surprisingly has not yet been evaluated in AD. Our preliminary data show that neural stem cells rescue cognitive deficits in our animal models of AD and neurodegeneration. Remarkably, the mechanism underlying the improved cognition involves production of a neurotrophin, which are a family of proteins that induce and support the survival, development and overall function of neurons. In particular, our studies point to “brain-derived neurotrophic factor” (BDNF) as the key mediator of the benefits produced by the neural stem cells. Hence, the questions we are addressing are unique, as they will inform us whether neural stem cell transplantation offers a viable approach to treating AD or whether BDNF alone is better. A better understanding of the mechanism(s) by which stem cell transplantation improves cognitive function would undoubtedly lead to the identification of novel and more clinically applicable pharmacological approaches to treat the cognitive dysfunction. There are two specific aims that will occur: 1. Aim 1 will determine whether BDNF is sufficient to restore cognition in a mouse model of neurodegeneration. 2. Aim 2 will determine if BDNF is necessary to restore cognition. 3. Aim 3 will determine if the benefits of stem cells can be extended or improved by also selectively degrading the plaque protein, amyloid beta. Accumulation of amyloid beta is a hallmark of Alzheimer’s disease, and is the target of several drug discovery efforts.

Progress Updates:

Dr. LaFerla’s team is currently investigating the benefits of stem cell transplantation for treating Alzheimer disease, and the roles played by a growth factor called BDNF. These researchers learned that transplanted nerve stem cells support the formation of new connections between host brain cells. Their studies demonstrate that strengthening these connections can reverse memory losses in Alzheimer disease mouse models. The team is continuing to explore new approaches to strengthen these connections over the long term.