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Antibiotic Shows Promise as Stroke Treatment
Date:10/1/2007

Minocycline improves patient outcomes if given with 24 hours, study finds

MONDAY, Oct. 1 (HealthDay News) -- An antibiotic used to treat severe acne and urinary tract infections also appears to be a potent weapon against acute ischemic stroke, a new report from Israeli researchers suggests.

Perhaps the best news about this discovery is that it widens the window of treatment for stroke from a few hours to 24 hours, experts say.

Though it is too early to change patient care, should the results be confirmed in larger, placebo-controlled, double-blinded clinical trials, "it will be probably one of the most used and effective treatments of ischemic stroke that we have," said Dr. Argye Hillis, a professor of neurology at the Johns Hopkins University School of Medicine in Baltimore.

The drug in question is minocycline, a tetracycline derivative that has been used for years to fight bacterial infections. Over the past decade, the drug has also been shown to be effective in animal models of several neurological conditions, including Parkinson's, Huntington's and Lou Gehrig's diseases.

Dr. Yair Lampl, of Tel Aviv University, and his colleagues randomized 152 patients with acute ischemic stroke into two groups, one of which received 200 milligrams of minocycline a day for five days, while the other was given a placebo. Treatment was initiated between six and 24 hours after stroke onset.

At one week, one month and three months following stroke, patient recovery was significantly improved in the antibiotic group relative to the control group on each of three tests that collectively assess neurological damage due to stroke and the patient's ability to perform daily tasks such as grooming, dressing and going to the bathroom.

"Statistically, there's a pretty marked difference between the groups," said Dr. Eric Smith, associate director of Acute Stroke Services at Massachusetts General Hospital in Boston. "Clinically, it is the difference between someone who looks almost normal compared to someone with more mild-to-moderate impairment due to stroke."

The findings were published in the Oct. 2 issue of Neurology.

This study focused specifically on ischemic stroke, the kind that is induced by clots that cut off blood flow to parts of the brain. According to Smith, minocycline appears to act as a neuroprotectant -- that is, as a compound that protects the brain from the resulting lack of oxygen and glucose, thereby allowing more brain tissue to survive.

Yet it is not at all clear just how minocycline does this, though several possible mechanisms have been proposed. Lampl suggested the effect "is at least partially dependent" on minocycline's ability to limit inflammation and apoptosis, or cell suicide.

Hillis said she found the results "potentially very exciting," both because of the magnitude of the effect, and because it was observed with a treatment that could be administered as much as a day after a stroke attack.

"They included patients who were eight to 24 hours after onset of stroke, on average 12 hours," she noted. "That's exciting, because that's about when most patients come to the hospital."

Most stroke treatments are now only effective within a few hours of stroke onset, Hillis explained. It's a therapeutic window that is too short to be effective for many patients.

Yet Hillis said she was not yet prepared to change the way she treats her own patients.

"I think this is very promising, very exciting, as a pilot study, but it's not enough to start treating people with minocycline," she said.

Smith concurred, saying, "I think this looks like a promising treatment with pretty big differences in outcome between the minocycline-treated and control groups. However, it is an early-phase study, and the results have to be considered preliminary. The field needs a larger, double-blinded study to confirm these findings."

In a double-blinded study, neither the treating physician nor the patient would be aware which treatment the patient was receiving.

According to Lampl, a larger study is being planned to address this concern.

More information

For more information on minocycline, visit MedlinePlus.



SOURCES: Yair Lampl, M.D., Department of Neurology, Edith Wolfson Medical Center, Holon, Israel; Eric Smith, M.D., M.P.H., FRCPC, assistant professor, neurology, and associate director, Acute Stroke Services, Massachusetts General Hospital and Harvard Medical School, both in Boston; Argye Hillis, M.D., professor, neurology, Johns Hopkins University School of Medicine, Baltimore; Oct. 2, 2007, Neurology


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