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2015 Grants - Sumbria
A Brain-Penetrating Biologic TNF-Alpha Inhibitor for Alzheimer’s Disease
Rachita Sumbria, Ph.D.
Keck Graduate Institute
2015 New Investigator Research Grant
Can a novel molecule that inhibits TNF-alpha in the brain reduce inflammation and nerve cell damage in Alzheimer’s disease?
TNF-alpha is a protein that plays an important role in the normal function of the immune system, but excessive levels of TNF-alpha can cause inflammation that damages cells. High levels of TNF-alpha are found in the brains of people with Alzheimer’s and this may contribute to nerve cell damage and cognitive problems. Drugs that inhibit TNF-alpha activity may have therapeutic benefit, but those currently available cannot cross the blood-brain barrier. The blood-brain barrier is a specialized structure that separates the brain from the blood circulation and controls the flow of molecules (e.g. drugs, nutrients) into and out of the brain.
Rachita Sumbria, Ph.D., and colleagues have used molecular techniques to develop a new drug candidate that inhibits TNF-alpha and is able to cross the blood-brain barrier. Initial studies using nerve cells grown in laboratory dishes and fruit flies have shown this experimental drug decreases the levels of inflammatory molecules, prevents nerve cell damage, and reduces levels of beta-amyloid, the protein fragment that accumulates into plaques in the Alzheimer’s brain. More extensive animal studies are needed to determine if this molecule may be useful for treating Alzheimer’s disease.
Dr. Sumbria’s research team plans to test the experimental TNF-alpha inhibitor in mice genetically engineered to develop an Alzheimer’s-like condition. They will administer the drug and measure the levels of inflammatory molecules and beta-amyloid in the brain, and assess the animals’ learning and memory function.
This research will allow scientists to further determine if inhibiting TNF-alpha activity in the brain may be an effective way to treat Alzheimer’s disease. If successful, these findings can help provide the framework to move this novel drug candidate toward human clinical trials.