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Nanoknitting Operation Restores Hamster SightMore Testing Required Before Trials on Humans

By Carey Goldberg

In work that may hold promise for victims of spinal cord and brain injuries, researchers report that they have managed to restore sight to blinded hamsters using a process they call nanoknitting.

The work represents the first time that nanotechnology - engineering on an ultra-tiny scale - has been used to fix brain damage, said Rutledge Ellis-Behnke PhD ’03, a neuroscientist at the Massachusetts Institute of Technology and the lead researcher on the paper.

It will be years before the knitting technique can be tried in humans, and it must still prove its worth in other animal experiments. But Ellis-Behnke said he hopes it can someday serve as part of a multipronged therapy to help regenerate nerve connections in the millions of people who suffer strokes, spinal cord damage, and brain injuries, particularly those whose brain injuries leave them “no longer the person that was before.”

“Our goal is to try to reconnect disconnected parts to restore that person as much as possible,” he said.

The researchers injected nanofibers into the gap created by cutting the neural pathway that enables vision. These fibers linked themselves together into a tiny scaffold that apparently helped heal the brain tissue and let axons - the transmission lines that connect neurons - regrow.

The knitting technique offers a possible way to overcome a formidable problem: When neural connections in the brain or spinal cord are damaged, they don’t tend to heal, which can result in lifelong brain damage and paralysis. When a neuron is cut, Ellis-Behnke said, it sprouts a “growth tip,” like a tree whose branch has been cut, but then the growth stalls. Researchers are trying to figure out why, and what they can do to spur more growth.

In the current work, Ellis-Behnke theorizes that either the nanoparticles block signals that trigger an immune response or they coat the growing tip of the axon, blocking the signals that tell them not to grow.

In recent years, scientists have chipped away at the problem of regenerating neural connections. There is growing consensus that there will be no magic bullet that addresses all these problems. Instead, scientists are investigating multiple strategies, each designed to address a different challenge.

Some examples of recent progress, as singled out in a report just released by the nonprofit Dana Alliance for Brain Initiatives:

Using an enzyme to encourage growth of the neuron and special cells to guide and structurally support that growth improved the recovery of rats with severed spinal cords.

A mix of stem cells and gene therapy targeted at rebuilding myelin also improved the recovery of rats with injured spinal cords.

A growing understanding of what blocks regrowth - including a protein called “Nogo” - has led to several possible countermeasures.

Also, scientists have been experimenting with “growth factors” to boost nerve regrowth in adults.

Ellis-Behnke’s work, published online last week in the Proceedings of the National Academy of Science, adds another possible tool, said several scientists familiar with the work but not involved with it.

The neuroknitting appears “very helpful” for brain repair, and “I think if they can do it in the spinal cord, it may be wonderful,” said Tatfong Ng, a researcher at the Schepens Eye Research Institute in Boston.

The knitting “could be very useful in combination with other treatments,” said Wolfram Tetzlaff, associate director of discovery science ICORD, the International Collaboration on Repair Discoveries in British Columbia, which focuses on spinal cord injuries.

However, he said, the hamster work involved a “clean knife cut” across the optic nerve, and “this is not how injuries typically present themselves.” Usually, neural connections torn by a stroke or a car accident, for example, tend to be much messier and thus harder to bridge.

Repairing clean cuts could be extremely useful, though, for stemming the harm from brain surgery, in which a surgeon’s scalpel leaves collateral damage every time it cuts into the brain. Ellis-Behnke, who also works for the University of Hong Kong Medical Facility, says he believes that within three to five years, it could be possible to start experiments with the nanoknitting material during human brain surgery.

“Every time you cut the brain, you’re disconnecting things, and that disconnection has never healed in the past,” he said. “We’re not only healing it, we’re getting regeneration, and we’re getting return of function.”

One appealing feature of the nanomaterial is that it is biodegradable and apparently poses no danger of contamination or inflammation inside the brain or spinal cord.

The nanoknitting work did not totally cure the blind hamsters. But the nanomaterial, injected within an hour after the visual pathway was cut in 16 adult hamsters, appeared to reduce the gap within the first 24 hours, and the axons regrew through the center of the cut.

When tested, three-quarters of those hamsters could see, as judged by whether they turned toward a nearby seed. None of the 31 blinded adult hamsters who had not received the nanosolution regained their sight.

For all the drama of restored vision, Ellis-Behnke emphasized that nanoknitting “is not a panacea.”

“We think it will take several other things, and we don’t even know if this is the best,” he said.

One of his next areas of research, he said: Exploring whether the nanomaterial can be helpful long after the nerve damage has occurred, which would make it useful to people who already suffer from spinal cord or brain damage.