Drug found to limit stroke damage
Administering the antibiotic minocycline within 24 hours after a stroke significantly reduces brain damage and physical impairment, Israeli researchers reported.
Researchers hope the drug, which also combats inflammation, may widen the “golden window” during which strokes can be treated.
Clot-dissolving drugs -- the current gold standard for stroke treatment -- must be administered in the first three hours to be effective, and many patients do not receive them in time.
If the study can be replicated, “minocycline could be an important means of reducing the disabling effects of stroke,” said Dr. Steven V. Pacia, a neurologist at Lenox Hill Hospital in New York, who was not involved in the study.
The findings, published today in the journal Neurology, will not change clinical practice anytime soon, said Dr. John R. Marler, associate director for clinical trials at the National Institute of Neurological Disorders and Stroke. “They were looking for signs that it might be effective, and they concluded that it might be. We need a larger trial” to be sure, he said.
The findings have nothing to do with infections, even though the drug is an antibiotic. Rather, the drug’s anti-inflammatory properties may block damage to neurons from toxins released when other brain cells die, said Dr. Raymond A. Swanson of UC San Francisco.
Swanson has previously shown in the test tube that minocycline blocks the activity of an enzyme called poly(ADP-ribose) polymerase-1, which can trigger inflammation and cell death.
The antibiotic is being studied in a variety of trials to determine whether it can protect brain cells in Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and traumatic brain injury, Swanson said.
Dr. Yair Lampl and his colleagues at Tel Aviv University studied 152 men and women who had suffered a stroke but arrived at the hospital too late for clot-dissolving therapy. They excluded those who had already shown signs of recovery, had other neurological disorders, had infectious diseases requiring antibiotic therapy or had a known allergy to tetracycline antibiotics.
Half received minocycline an average of about 12 hours after their strokes and for five days afterward; the rest received a placebo. Doctors and patients knew who had received the drug, but the neurologists evaluating the patients’ conditions did not.
“The improvement was apparent within a week of the stroke,” Lampl said. At the end of three months, those receiving minocycline did four times better on the National Institutes of Health stroke scale, which measures vision, facial palsy, movement and speaking ability.
The minocycline group had a score that indicated little or no disability, and the placebo group was at the high end of mild disability, the team said. Similar results were obtained on two other ratings scales.
That is “a relatively dramatic improvement,” Marler said. “But they knew they were getting the drug, and the people who didn’t get the drug knew that they weren’t getting it.”
Also, he added, “These were relatively mild strokes, and we would have expected [the control group] to get better than they did.”
Researchers are planning a larger blind study in which participants won’t know they are getting the drug, Lampl said. The team would also like to determine whether giving the drug intravenously would be more effective than giving it orally.
None of the researchers reported any conflicts of interest. Minocycline is a generic drug that is widely used to treat acne, and it is generally considered safe.
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