Experimental drug helps the brain recover from stroke -- in mice

Scientists have developed a “proof of concept” drug for stroke patients that helped afflicted mice recover the ability to walk normally. In laboratory experiments, the researchers also found biological evidence that the drug helped grow new neurons in the brain, according to a study published online Tuesday by the journal Stroke.

An estimated 795,000 Americans have a stroke each year, according to the National Stroke Assn. in Centennial, Colo. They occur when the brain is suddenly deprived of oxygen and nutrients, either by a blockage in a vessel (which causes an ischemic stroke) or due to a burst vessel that causes bleeding in the brain (a hemorrhagic stroke). Either way, a stroke can leave patients with weakness or paralysis on one side of the body and “cause problems with thinking, awareness, attention, learning, judgement, and memory,” among other problems, according to the National Institute of Neurological Disorders and Stroke.

Though stroke is a major cause of long-term disability, the only proven treatment for patients is to dissolve a clot or stop the bleeding in the brain while the stroke is happening. Once it’s over, doctors and therapists can only offer rehabilitation to minimize the damage. The experimental drug being developed by scientists from Stanford University School of Medicine, Weill Cornell Medical College and UC San Francisco aims to change that.

The drug is designed to mimic a protein called brain-derived neurotrophic factor, or BDNF, which is thought to help stimulate growth of new neurons and make the brain “plastic,” or able to adapt to changes. BDNF works in cooperation with a receptor in the brain called TrkB. So the scientists set out to find a way to activate TrkB in hopes that doing so would mimic the action of BDNF and promote actual healing in the brain.

The researchers turned to a small molecule called LM22A-4 that – like BDNF – is known to bind to TrkB. The compound was made by a company called Ricerca Biosciences.

To test its stroke-healing powers, the research team used 4-month-old mice and trained them to perform several physical tasks. Then they induced strokes by blocking the right carotid artery in the animals. This caused the mice to perform worse on tasks that they used to do with ease, such as walk across a horizontal ladder and keep their balance on a spinning rod (picture a lumberjack in a log-rolling competition).

Three days after the strokes, some of the mice were treated with LM22A-4, delivered through their noses, while others got a placebo. Mice in both groups recovered well enough to walk across a horizontal ladder, but the animals that got the experimental drug recovered significantly faster, according to the study.

Looking at another mobility measure, the researchers found that the mice in the placebo group saw their “swing speed” decline by 50% and stay there. But mice who got LM22A-4 were able to regain their pre-stroke swing speed.

In the brain itself, the scientists found twice as many new neurons growing in the treated mice compared with their untreated counterparts. Those extra neurons were concentrated around the site of injury, according to the study.

Not only did LM22A-4 help, it did so without causing any harm. The researchers said the drug did not prompt scar tissue to form, boost inflammation or affect the growth of new blood vessels, among other things.

A summary of the study is available online here.

UCSF and the University of North Carolina have already patented the use of LM22A-4 for stroke treatment. One of the Stanford-based study authors has formed a company that is working to turn LM22A-4 and other small molecules into drugs to treat neurological disorders. Of course, any treatment for human stroke victims is still years away.

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