The Use of Adult Bone Marrow Stem Cells in Treating Alzheimer's Disease

Bruce Cohen, MD, PhD
McLean Hospital (Belmont, MA)

Co-Principal Investigators

Kai Sonntag, MD, PhD
McLean Hospital
Year Awarded:
2008
Grant Duration:
April 1, 2008 to November 30, 2010
Disease:
Alzheimer's Disease
Award Amount:
$150,000
Grant Reference ID:
A2008319
Award Type:
Pilot
Award Region:
US Northeastern
In Memory of Dr. Anne Cataldo

A Novel Treatment Strategy for Neurorepair in Alzheimer's Disease

Summary

In this project, 'adult' stem cells will be used as a delivery system to deliver sAPP to brain regions undergoing neurodegeneration. The hypothesis is that sAPP will work together with growth factors to protect and repair cholinergic neurons in the brain, thereby representing a potential for therapeutic treatment in humans with AD.

Details

Research Updates

We began looking at novel means—namely the delivery of growth factors by stem cells—for brain cell protection or regeneration, using stem cells derived from the bone marrow of adults, called multipotent adult progenitor cells (MAPCs) or mesenchymal stem cells (MSC). Our studies thus far show that new and selective nerve cell growth can be encouraged from MAPCs, and importantly that these cells have the ability to generate the same types of nerve lost in AD. MSC are autologous, meaning these cells can be obtained from the marrow of the same individual with AD. Patients thus serve as their own donors, eliminating the occurrence of a graft-host rejection – an immune response that often occurs with the transplantation of tissue obtained from one individual to another. MSC also can be delivered to brain through intravenous injection, which we have observed in our animal studies.

Despite previous reports that MSC can form nerve cells, our studies confirmed growing evidence that this potential is greatly limited. In addition, delivery of MSC to the brain has proven to be very inefficient with poor long-term survival of the new cells. While we work on improvements in the source or choice of stem cells, we have developed and are testing a new strategy to test the original hypothesis, that the delivery of sAPP to the brain will have neuroprotective effects. Using a virus vector-based gene therapy approach, we have demonstrated that viruses produce high amounts of sAPP both in cultured cells and when injected into the brain of test animals. We are evaluating whether this novel strategy will arrest neurodegenerative processes in animal models of AD. This approach can be applied with viruses that cause long term increases in the production of growth factors and can be combined with the use of MSC or other stem cells to protect or repair brain tissue. Our hope is that results from this alternative approach could have important implications for the development of future therapies for AD. Early results are promising, as noted.
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