For more than a decade, scientists have searched for a drug that could be given in the hours immediately after a stroke to protect and preserve neurons in blood-starved areas of the brain.
An intriguing study published Tuesday suggests that a common antibiotic used to treat conditions ranging from acne to respiratory infections could have such brain cell-saving properties even when it is administered up to 24 hours after stroke symptoms begin.
While doctors said more research is needed to confirm the study's results, the already established safety record of the drug minocycline as an approved antibiotic now may prompt some physicians to use it as a so-called off-label treatment for stroke.
"I guess if I had a stroke, I would take minocycline on the way to the hospital," said Dan Heffez, a neurosurgeon with the Milwaukee Neurological Institute.
Heffez and several other physicians not associated with the study said the findings could be of huge importance in the quest to find so-called neuroprotective drugs that can preserve neurons and other brain cells in strokes, traumatic brain injuries and other neurological disorders.
"It's a cheap drug," Heffez said. "It's been around for a long time. It has a great safety profile."
The study involved 152 stroke patients who were treated at a hospital in Israel. The study was initiated by the hospital, the Edith Wolfson Medical Center, and Tel Aviv University and was not funded by a pharmaceutical company. The study was published in Neurology, the journal of the American Academy of Neurology.
The patients in the study were not eligible to receive the first-line stroke treatment of the clot-dissolving drug tPA (tissue plasminogen activator). The IV medication generally must be given within three hours of the onset of stroke symptoms, because the increased risk of bleeding in the brain associated with tPA eventually outweighs the odds that the drug will significantly reduce the patient's disability.
Compared with tPA, minocycline "demonstrated an efficacy of a much longer period," said lead author Yair Lampl, a physician in the hospital's neurology department. "I think both methods can be complementary."
The new study was designed so the patients could get oral minocycline or a placebo between six and 24 hours after their symptoms began and continue either one for five days. The patients then were evaluated up to three months later by standardized tests that measure disability and other neurological deficits.
On the main measure of study, the National Institutes of Health Stroke Scale, those who got minocycline had an average score of 1.6, indicating little or no disability, compared with a score of 6.5 in the placebo group, which indicates the high end of mild disability.
Doctors offered a range of opinions on whether minocycline could be used now as an off-label treatment on a case-by-case basis until a larger, more rigorous trial can be done.
"Since it's relatively innocuous, (doctors) will do that," Heffez said. "Whether that is wise is unclear."
Doctors already use too many off-label treatments, especially in neurology, said John Marler, associate director for clinical trials with the National Institute of Neurological Disorders and Stroke, part of the NIH.
"This does not give us an excuse for not rushing to the emergency room," Marler said. "The real danger is that it could lead physicians to be complacent."
He said that while the study offered "a very hopeful sign," its design was such that the findings may not be real.
He noted that the study was designed as an open-label trial, meaning that patients knew if they were getting the drug, but doctors who later evaluated their condition did not know.
The magnitude of the drug's benefit was "quite impressive," said Justin Sattin, an assistant professor of neurology and medical director of the stroke program at the University of Wisconsin Hospital and Clinics in Madison.
But he noted that at least one other potential neuroprotective drug showed an initial benefit that disappeared in a larger trial.
Sattin said he could not say whether minocycline will be used off label at UW Hospital - at least not until he and other stroke doctors have time to analyze the study. "There may be instances where we will," he said.
The other unanswered question about minocycline is how it works. Doctors said that whatever benefit the drug has in preserving brain cells likely is not due to an antibiotic effect.
Laboratory and animal research suggests that it may reduce inflammation in the brain or that it may act on brain cell genes that control a process known as apoptosis, in which cells are programmed to die.
If additional research shows that minocycline is effective, it might be tried as part of a cocktail approach that would include opening a blocked artery with tPA and using minocycline or another neuroprotective drug to preserve brain cells, said Ralph Sacco, a professor of neurology at the University of Miami and spokesman for the American Academy of Neurology.
"I think this (minocycline stroke study) is a new glimmer of hope that should be followed up," Sacco said. "It's something to be cautiously optimistic about."
Minocycline also is being tested in studies involving several other brain disorders, including multiple sclerosis, amyotrophic lateral sclerosis, regressive autism in children, cognitive impairment in AIDS patients taking antiretroviral drugs and cognitive deficits that can accompany surgery on the carotid artery.
