Fast action is needed to survive a stroke. Once brain cells die due to lack of oxygen during an ischemic stroke (a stroke caused by a blood clot), there’s no saving them, and reactive oxygen species released by the dying cells injure nearby brain tissue. A quick dose of the clot buster tPA can come to the rescue, but it has to be given within the first four hours after a stroke, and its use is limited because its blood-thinning effects are so powerful. It is not an option for patients who have high blood pressure, a history of bleeding or weak blood vessels. But a drug used to treat another serious health condition that works in an entirely different way may allow many more people to survive strokes with minimal disability.
TURNING AN AVAILABLE DRUG INTO A NEW LIFESAVER
The drug is retigabine (also called ezogabine, brand name Potiga), an antiseizure drug for certain forms of epilepsy. Researchers from the University of Texas studied its effects in mice that, for the sake of human health, were experimentally given either catastrophic strokes or less severe transient ischemic attacks (ministrokes). Mice given a single dose of retigabine after their strokes were compared with nontreated mice and mice that were not given strokes (controls). The treated mice were divided into groups and each given the drug at a different time, ranging from immediately to six hours after the stroke. Twenty-four hours after the strokes occurred, the mice that had had mini-strokes were tested for balance and coordination by having them walk on a balance beam and on a tiny ladder. (All of the mice had mastered these tasks before their strokes.) Since the mice that had had major strokes were not able to complete these tasks due to the severity of stroke injuries, they were not tested for motor function.
The results: The ministroke mice that didn’t receive retigabine slipped and fell several times, but the mice that did receive retigabine were able to traverse the balance beam and ladder just as well as control mice.
All the mice were then euthanized over a period of one to five days after their strokes so that the area of the infarct (the dead brain tissue resulting from the strokes) could be examined. All of the mice that had been given retigabine, whether for a mini-stroke or a major one, had much smaller infarcts than the mice that hadn’t been given the medication. Although the greatest benefits were found when the drug was used within three hours post-stroke, retigabine was effective when given up to six hours after the stroke. And even though the infarct size can continue to increase for days after a stroke because dying cells release destructive molecules, mice given retigabine showed no increase in infarct size, suggesting that the drug stops stroke damage in its tracks.
SOOTHES BRAIN CELLS
Retigabine treats epilepsy by reducing the electrical activity of nerve cells that are out of control because of excessive electrical firing during an epileptic seizure. The researchers theorized that retigabine may reduce damage to the brain in stroke patients by decreasing the excitability of the dying nerve cells and preventing the cells from firing when they really should be preserving their strength.
The researchers are not entirely sure that the drug will have the same effect in people as it did in mice, but retigabine has been on the market and used in humans since 2011 for treating epilepsy. Although the drug isn’t currently FDA-approved to treat ischemic strokes, doctors can use the drug off-label for conditions other than epilepsy and may consider doing so if evidence mounts about retigabine’s lifesaving potential. Like all drugs, it can cause side effects, which can include mild and temporary imbalance, drowsiness or confusion, vision loss, and pain or difficulty urinating. Whereas the drug is used on a daily basis in patients with epilepsy, it would be used, like tPA, as a one-time emergency medication in stroke patients and so any side effects would not persist longer than a day or two. However, the research suggests that the prevention of brain damage would be permanent. Thus the benefits will need to be weighed against risks as research about the drug for stroke patients continues.
In the meantime, researchers are planning clinical trials of the drug for stroke patients that will likely compare its effectiveness and safety to tPA. If you know that you are at high risk for stroke, you may want to speak with your doctor about participating in a clinical trial of retigabine and also discuss what emergency-care plan is in place for you should you have a stroke.