Researchers at Children's Hospital Boston have discovered a naturally occurring growth factor that stimulates regeneration of injured nerve fibers (axons) in the central nervous system.
Under normal conditions, most axons in the mature central nervous system (which consists of the brain, spinal cord and eye) cannot regrow after injury. The previously unrecognized growth factor, called oncomodulin, is described in the online edition of Nature Neuroscience.
Neuroscientists Yuqin Yin, MD, PhD, and Larry Benowitz, PhD, who are also on the faculty of Harvard Medical School, did their studies in the optic nerve, which connects nerve cells in the eye's retina to the brain's visual centers, and is often used as a model in studying axon regeneration.
When oncomodulin was added to retinal nerve cells in a Petri dish, with known growth-promoting factors already present, axon growth nearly doubled. No other growth factor was as potent. In live rats with optic-nerve injury, oncomodulin released from tiny sustained-release capsules increased nerve regeneration 5- to 7-fold when given along with a drug that helps cells respond to oncomodulin. Yin, Benowitz and colleagues also showed that oncomodulin switches on a variety of genes associated with axon growth.
Benowitz, the study's senior investigator, believes oncomodulin could someday prove useful in reversing optic-nerve damage caused by glaucoma, tumors or traumatic injury. In addition, the lab has shown that oncomodulin works on at least one other type of nerve cell, and now plans to test whether it also works on the types of brain cells that would be relevant to treating conditions like stroke and spinal cord injury.
The current study builds on work Benowitz, Yin and colleagues published a few years ago. Studying the optic nerve, they found - quite by accident - that an injury to the eye activated axon growth: it caused an inflammatory reaction that stimulated immune cells known as macrophages to move into the eye.
"To make this finding clinically useful, we wanted to understand what was triggering the growth, so we could achieve nerve regeneration without causing an injury," Benowitz says.
Working in Benowitz's lab, Yin took a closer look and found that the macrophages secreted an essential but as-yet unidentified protein. Further studies revealed it to be oncomodulin, a little-known molecule first observed in association with cancer cells.