Rewiring Job: Drug spurs nerve growth in stroke-damaged brains

A drug patterned after a naturally occurring biological chemical enables rats to regain movement in extremities paralyzed by a stroke, a U.S.–Canadian team reports. The compound, called inosine, induces nerve fibers to grow and reconnect in the brain and spinal cord, say the researchers.

The findings suggest that inosine could boost recovery in many of the 600,000 people in the United States each year who have a stroke. The scientists report their work in the June 25 Proceedings of the National Academy of Sciences.

The speech- and muscle-control problems that characterize the aftermath of a stroke arise when neurons, the primary cells of the brain and nervous system, lose their supply of blood and die. In a healthy brain, some neurons use long tendrils, or axons, to link to spinal cord neurons, which relay brain signals via their own axons to the rest of the body. When a brain neuron dies in a stroke, the connection is interrupted.

Larry I. Benowitz, a neuroscientist at Harvard Medical School and Children’s Hospital in Boston, and his colleagues simulated such damage in rats by shutting off blood flow to an area of the brain that controls limb movement on one side of the body. The researchers had previously implanted tiny pumps under the rats’ skin that could deliver a solution to the animals’ brains. Immediately after the strokes, the pumps began to deliver inosine in some of the rats and an inert solution of saline in the others.

After 1 week, the inosine-treated rats showed substantial recovery of leg movement and, by 3 weeks, had regained nearly all leg function. Saline-receiving rats made only half as much progress. The inosine-treated rats were also better able to retrieve food and swim at 4 and 8 weeks after the stroke, respectively.

Subsequent testing showed that inosine treatment spawned improvements even when started 24 hours after the stroke, suggesting that people diagnosed belatedly with stroke might still benefit from the drug, says study coauthor Marc Lanser, an immunologist at Boston Life Sciences, which holds a patent on the use of inosine in stroke recovery.

Subsequent analysis of the rats showed little axon regrowth on the damaged side of the brains. However, compared with the saline-receiving group, the inosine-treated rats had up to three times as many axons sprouting from healthy neurons on the other side of the brain. Those new axons seem to have established working connections with neurons in the spinal cord that had lost their previous hook-up, the researchers say.

Inosine switches on “a whole family of genes” associated with axon growth, Benowitz says. The chemical occurs naturally in small amounts in adult brains. While this concentration increases after injury and may help the brain to partially rewire itself, it appears insufficient for full recovery, says Benowitz. Up to 30 percent of stroke victims are permanently disabled.

“I think [inosine] has a lot of potential in human patients,” says Jon H. Kaas, a neuroscientist at Vanderbilt University in Nashville. “This clearly is solid research.”

Boston Life Sciences plans to start testing inosine in patients early next year.

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