Treatment with Transforming Growth Factor Alpha Restores Motor Function after Stroke

Positive results from two studies conducted in rats suggest that the small protein transforming growth factor alpha (TGF-alpha) has the potential to restore motor function in stroke victims as long as four months after the event.

Investigators at the University of California, Irvine (USA) worked with a rat stroke model where the disease was induced through a middle cerebral artery occlusion (MCAO). Treatment of the animals with TGF-alpha was either by direct delivery to the animals' brains (as described in the May 5, 2009, issue of the journal Neuroscience) or - mimicking a nasal spray - through the nose (as described in the January 11, 2010, online edition of the Journal of Stroke & Cerebrovascular Disease).

The earlier study found that direct injection of TGF-alpha into the brain restored nearly 90% of the paralyzed rats' motor function. Results of the latter study indicated that animals receiving the drug via the nose regained about 70% of motor function. Rats that did not receive treatment with TGF-alpha recovered only about 30% of motor function.

Examination of brain tissue from the paralyzed rats showed that TGF-alpha produced a massive proliferative response even when the growth factor was administered as late as four weeks after injury. The newly generated cells migrated preferentially along and ventral to the corpus callosum and external capsule to the site of the injury where many of them differentiated into several site-appropriate neuronal phenotypes in association with near complete (99%) behavioral recovery.

"No drugs exist that will help a stroke after a few days. If you have a stroke, you do not have many treatment options," said senior author Dr. James Fallon, professor of psychiatry and human behavior at the University of California, Irvine. "Now we have evidence there may be therapies that can repair damage to a significant degree long after the stroke. It's a completely unexpected and remarkable finding, and it is worth trying in humans."

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