2005 New Investigator Research Grant

Recent clinical trials have shown that if certain naturally occurring neuro-protective proteins can be placed at the correct site within the brain, they might slow or halt the progression of neurodegenerative diseases, including Alzheimer’s. However, there are numerous technical hurdles that must be overcome before this type of therapy can become mainstream, not least being a safe and efficient way to maintain delivery of the proteins to the nerve cells.

One solution may be to use gene therapy to get the neuroprotective proteins where they are needed. This technique involves placing the gene, or genetic blueprint, for the desired protein into a target cell, which can then start to manufacture the protein. David V. Schaffer, Ph.D., and colleagues plan to develop a safe and highly efficient gene therapy procedure that will target astrocytes, the helper cells of the brain. This approach may have advantages over targeting nerve cells directly. First, because there are about ten times more astrocytes in the brain than nerve cells, more neuroprotective proteins should be produced. Second, placing new genes in delicate neurons runs the risk of stressing and damaging the very cells that need to be protected.

Because there is currently no feasible means of performing gene therapy on astrocytes, Schaffer and colleagues will focus on modifying non–disease-causing viruses. These viruses have been shown in animal studies to serve as safe and efficient delivery vehicles to the brain. The scientists will modify the viruses so that they can bind to and deliver neuroprotective-related genes into astrocytes. They will assess whether the gene delivery system works in animals and results in astrocyte production of the neuroprotective protein in the brain. This work may lay a foundation for studying the utility of this method as an Alzheimer treatment.