Growth factors may improve
recovery from stroke, even days later

BOSTON — June 12, 1998 — One of the most promising approaches to limiting the immediate brain damage caused by strokes also may be able to enhance the brain’s ability to recover from stroke-related damage, even when given days or weeks after a stroke occurs, says Seth Finklestein, MD, director of the Central Nervous System Growth Factors Laboratory at the Massachusetts General Hospital (MGH). Speaking today at "Brain and Psyche 1998," a press seminar in Boston sponsored by the MGH, the Whitehead Institute and McLean Hospital, Finklestein described how neurotrophic growth factors have the potential of significantly reducing the disability caused by stroke.

"We know that some patients show recovery from stroke, at least partially regaining abilities like speech and motor strength that are lost when brain tissue is destroyed. And it appears that this recovery is accomplished through other, undamaged parts of the brain compensating and taking on new functions," Finklestein said. "Our work with animals has shown that administering these growth factors in the days after a stroke can significantly improve the recovery process. They appear to help the brain do what it does best – to learn."

More than 500 thousand Americans experience a stroke each year, one quarter of them under age 65. Two-thirds of them survive their strokes and go on to live an average of seven years, often with serious sensory, motor or cognitive disabilities. More than two-thirds of survivors are unable to return to full-time employment

Studies in mice by Finklestein and his colleages have focused on two growth factors: basic fibroblast growth factor (bFGF) and osteogenic protein-1 (OP-1). While originally discovered through their abilities to promote growth of connective tissue cells and bone, respectively, both naturally-occurring factors have been found to be active in the developing brain and to promote growth of and connections between nerve cells. They also are produced in small quantities in brain tissue near the area of a stroke, suggesting they may have a role in the natural recovery process.

Finklestein’s team has been studying bFGF for several years and defined its ability to limit the immediate damage caused by a stroke when given within hours of the original event. Based on their pioneering animal work showing that the area of damage is much smaller in rats receiving the growth factor, bFGF is now being tested for treatment of acute stroke patients in large-scale clinical trials.

More recently, the MGH researchers have published several animal studies showing that growth factors can improve recovery of function in rats. Two studies – a 1997 paper involving bFGF and a 1998 paper involving OP-1 – showed that injection of the growth factors into the spinal fluid of rats starting at one day after experimentally-induced strokes resulted in significantly greater recovery of motor and sensory function of the affected limbs than seen in rats injected with a control substance. Chemical analysis showed an increased level of a protein (GAP-43) known to be involved in the growth of nerve cell connections.

"We’re now getting ready to start testing growth factors to enhance recovery in stroke patients," Finklestein said. "If this strategy is successful, it will greatly expand our opportunities to help patients, many of whom do not seek medical care in the hours immediately following their strokes because their symptoms are not recognized.

"Our nursing homes and long-term care facilities today contain thousands of patients disabled by strokes," he continued. "What if we could make them better? The overall impact could be huge."

Contact Sue McGreevey in the MGH Public Affairs Office.

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