NIH grant supports development of a novel drug for stroke treatment

Physical and Biological Sciences News

Most strokes occur when a blood vessel carrying oxygen to the brain is blocked by a blood clot. A drug called tissue plasminogen activator (tPA) can dissolve the clot and restore blood flow, but only a small percentage of stroke patients get this treatment due to the risks associated with it. Stroke is currently the fifth leading cause of death and the leading cause of long-term disability in the United States.“There’s clearly a big need for a novel stroke drug,” said Theodore Holman, professor of chemistry and biochemistry at UC Santa Cruz.
Holman has been collaborating with Klaus van Leyen at Massachusetts General Hospital to develop a new type of drug that can protect brain cells from the damaging effects of a stroke. When a stroke interrupts the flow of blood in the brain, the affected area of the brain is deprived of oxygen and brain cells begin to die. Abilities such as movement or speech that were controlled by the damaged parts of the brain are then impaired, sometimes permanently.
But if blood flow and its associated oxygen are restored fast enough, the patient enters a “grey zone” where doctors could potentially rescue the brain tissue, Holman said. That grey zone is where his team’s new drug, called ML351, comes in.
ML351 works to inhibit an enzyme known as 12/15-lipoxygenase, which is produced in large amounts when brain tissue is under oxidative stress. Lipoxygenase, which Holman has been studying since 1993, is a major contributor to irreversible cell death during strokes. By inhibiting the enzyme’s activity in the aftermath of a stroke, the new drug treatment could protect brain cells and reduce the amount of damage in the brain.
“We can induce strokes in mice, and if we give them our drug, we can reduce the damaged area by 40 percent,” Holman said. “Even lowering damage by 20 …

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