UCSF scientists develop novel strategy for nerve repair

October 2005 issue of Neurosurgery -----

Using the latest advances in microtechnology, a team of UCSF scientists has developed a novel strategy for repairing the nerve damage that occurs in injuries to the nervous system.

The scientists, in conjunction with scientists elsewhere, have also developed a device to carry out the approach, which involves conducting microsurgery at the molecular level of the cell.

The technique, reported in the October issue of Neurosurgery, involves surgically replacing damaged axons—the long, fragile fibers that conduct impulses between nerve cells in the brain, spinal cord and limbs—with healthy ones.

The signaling that axons, which are approximately one-fiftieth the thickness of a strand of human hair, support between nerve cells is the fundamental form of communication in the body. When that communication breaks down, as it does in nerve injuries, the results can range from pain to movement disorders to paralysis.

The current approach to treating damage to the nervous system has limited success. With injuries to the peripheral nervous system—which extends throughout the body, beyond the brain and spinal cord—surgeons sew the nerve connective tissue back together in the hope that the axons will regrow and eventually find their way back to their targets. The success of regrowth can be unpredictable and can take one to two years, and the degree of functional recovery from severe injuries is marginal.

With injuries to the central nervous system—the portion of the nervous system consisting of the brain and spinal cord—no axon regrowth is possible and the resulting disability is permanent.

The strategy being explored by the UCSF-led team involves directly repairing and reconnecting the severed ends of axons. In the current study, the team reports successfully cutting, removing, and repairing non-human axons in the culture dish using microdevices they developed, including an axon nanoknife.

The nanoknife was invented jointly by UCSF scientists and MEMS Precision Instruments. The intellectual property originating from the UCSF portion of the invention belongs to the Regents of the University of California. The UCSF scientists have no financial interest in the device.
“The surgical repair of individual axons has not been explored previously because the manipulation of such small biological entities has been beyond the capabilities of existing microsurgical techniques,” says the senior author of the study, David Sretavan, MD, PhD, UCSF professor of ophthalmology and physiology, and a member of the neuroscience and bioengineering programs. “However, our research is beginning to indicate that a number of core microtechnologies can be used to carry out the basic steps of direct axon repair.”

The new strategy, he says, could ultimately improve the quality of life for people who suffer from spinal cord injury and other nerve injuries.  There are 11,000 cases of spinal cord injury a year in the United States, and the cost of treatment for individual patients ranges from $2 million to $6 million each.

One consequence of nerve injury is the development of Wallerian degeneration, which occurs within 24 to 48 hours of a severe trauma to the nerve, when the part of the axon that has become dissociated from the nerve body degenerates and dies, taking the synapses with it. By intervening before the onset of Wallerian degeneration, says Sretavan, scientists may be able to save those synapses and help patients recover more function.

The axon nanoknife has an ultra-sharp edge that is just 20 nanometers wide, about 2 percent the width of an average axon.  The knife is constructed from a thin silicon nitride membrane and is effectively transparent, allowing the optical monitoring of axons during the cutting procedure. The prototype axon nanoknife is directed using a standard micromanipulator, currently available in most bioresearch laboratories.

The next step in further refining the axon repair technology, Sretavan says, is to develop a “smart knife,” which will contain an on-board actuation or force generation mechanism to deliver precise cutting strokes without the need for direct human operation.

Co-authors of the study were Wesley Chang, PhD, of UCSF; Christopher Keller, PhD, of MEMS Precision Instruments, Richmond, CA; and Michel Kilot, MD, of the University of Washington.

The research was funded by That Man May See, Inc., and the Sandler Family Supporting Foundation.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.