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Cancer Drugs May Help Nerves Regrow
6 October 2005 (All day)
The central nervous system in adult mammals is notoriously bad at healing itself. Once severed, the axons that connect one neuron to another can't regrow. That's why people regain little, if any, movement or sensation after a spinal cord injury. Now, researchers have made a promising discovery. In the 7 October Science, they identify a class of drugs--including one already on the market for treating cancer--that promote axon regeneration in rodents.
In the new study, Zhigang He, and Vuk Koprivica at Children's Hospital in Boston along with colleagues tested about 400 small molecules on cultured rodent neurons, hoping to identify ones that promoted the growth of new axonlike extensions. Most of the compounds did nothing, but several compounds that blocked a cell surface protein called the epidermal growth factor receptor (EGFR) had impressive effects.
To test the compounds on nerve injuries in live animals, the researchers crushed an optic nerve in adult mice then packed the nerve with foam soaked with one of the EGFR blockers. Two weeks after the injury, the treated mice showed a ninefold increase in axon regeneration compared to untreated animals. Additional work by He's team suggests that the compounds block two kinds of molecular signals: inhibitory molecules embedded in the myelin insulation on axons and inhibitory signals spewed out by support cells that form a scar around the site of injury.
"It's a really unexpected finding," says Marie Filbin, a neurobiologist at Hunter College in New York City. She and other experts say they never suspected that EGFR might have a role in thwarting regeneration. The study "identifies a novel target for therapeutic interventions," Filbin says. Even more exciting, says Ben Barres, a neurobiologist at Stanford University in California, is that drugs that inhibit EGFR signaling are already approved for treating lung cancer, raising the possibility of a quick transition from lab to clinic. Indeed, He's team reports that one such drug, Tarceva, made by Genentech in South San Francisco, California, promoted regeneration in cultured neurons. Genentech is now testing Tarceva in a mouse model of spinal injury.
But EGFR blockers alone may not be enough to cure spinal injuries, He cautions. Compounds that actively promote axon regeneration may be needed as well. As with driving a car, He says, taking your foot off the brake only gets you so far--then you need to hit the gas.