Nerve protector could make for new stroke treatments

La Jolla, Calif. A research team lead by the Burnham Institute has synthesized and tested a new series of inhibitors that can prevent the type of nerve cell injury and death associated with many neurodegenerative diseases and stroke. The study, led by Stuart Lipton, MD, PhD, professor and director of Burnham's Del E. Webb Center for Neuroscience and Aging Research, is published in the July issue of the Journal of Neuroscience.

There is but one medical treatment approved for stroke, the third leading cause of death in the United States: tissue plasminogen activator ("tPA"). tPA must be administered within 3 hours of stroke onset to restore the flow of blood to the brain. Unfortunately, treatment with tPA can also contribute to nerve cell damage. In recent years, medical scientists have begun to understand that tPA activates an entire family of enzymes, called matrix metalloproteinases, that normally regulate how cell structures are held together.

Dr. Lipton, together with first author Dr. Zezong Gu, and other colleagues at Burnham, University of Notre Dame, and Wayne State University in Detroit, have found that a molecule called SB-3CT blocks the activity of one member of the metalloproteinase family, called MMP-9.

Previous work at Burnham and elsewhere has shown that damage to the brain triggers excessive activity among MMPs, especially MMP-9. The enzymes degrade cell structures, inducing cell death and escalating brain damage in mice. In the current study, the researchers determined the particular mechanism of action for MMP-9. In doing so, they identified a new drug target and, armed with this knowledge, generated a lead therapeutic compound, SB-3CT.

"MMPs have been targeted for stroke therapy, but other drugs have had side effects," said Lipton. "This was due to the fact that therapies hit all MMPs, and not just the ones causing the nerve cell damage. Additionally, previous drugs had side effects on other organs in the body. He

Contact: Nancy Beddingfield
Burnham Institute

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