A $1.3 million grant from the National Institute of Neurological Disorders and Stroke could help Houston Methodist scientists better understand how the body's own immune system drives multiple sclerosis.
The five-year project will be led by Todd Eagar, Ph.D., an immunologist in the Department of Pathology and Genomic Medicine at Houston Methodist Hospital. Eagar is also the associate medical director of the Histocompatibility and Transplant Immunology program.
Using a model of multiple sclerosis (MS), Eagar's group will examine how two important cellular systems spur the development of MS. Eagar will also look at how these two systems affect the behavior of T and B cells, immune system stalwarts that in MS become inflammation-causing, autoimmune culprits of brain cell degeneration.
Past studies by Eagar and others suggest that dismantling either the Notch signaling pathway or a protein complex called gamma secretase can decrease the severity of MS symptoms in animal models. Notch is used by most cells, including T and B cells, for cell-cell communication. Gamma secretase turns on Notch. Eagar believes Notch may be at least partly responsible for T and B cell malfunction, and that suppressing gamma secretase -- thereby preventing Notch from being switched on -- might be the key to limiting MS-related damage.
"We think gamma secretase is important for T and B cells to talk to each other," Eagar said. "This project will look at how the interactions between T and B cells promote inflammation. We are very interested in how we can use drugs like gamma secretase inhibitors to suppress the immune system during phases of inflammation."
The present NIH-funded project will also help the scientists determine whether Notch and gamma secretase may be adequate drug targets in future human clinical trials.
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