New surgery heals nerve damage in weeks

THE once paralysed limb began to twitch just minutes after the operation. It was an early sign that the rat was on a fast track to recovery that would see it up and running within weeks.

The rodent is one of more than 200 to have undergone a new surgical procedure for nerve repair that provides faster - and better - results in animals than existing techniques. The crucial question is: can it work as well in humans with the sorts of injuries that the real world inflicts upon us?

"In animal models, the results are better than any current techniques used for nerve repair," says Wesley Thayer of Vanderbilt University in Nashville, Tennessee, a member of the team behind the new procedure.

So far, Thayer and team leader George Bittner of the University of Texas at Austin have used the new technique to treat rats after severing their sciatic nerve, which mediates leg movement and feeling. With plans afoot to begin clinical trials and work also under way to see if the procedure can heal spinal cord injuries in rats, nerve specialists are cautiously optimistic that Bittner and Thayer are on to something.

When a nerve is severed through injury, surgeons must suture the two stumps together as quickly as possible. Yet even under controlled lab conditions, Bittner's tests in rats suggest that these conventional sutures restore little more than 30 per cent of previous mobility, even three months after surgery. His new technique helps to restore twice that, in as little as two weeks. The secret, he says, is to prevent the body lending a helping hand.

Put bluntly, the body botches nerve repair. It forms seals over the two severed stumps of a broken nerve within an hour, says Bittner, but it doesn't reconnect them first. Even if surgeons then suture the two ends, the seals will prevent nerve signals from passing easily across the join (see "Bound together").

Bittner realised that we need a system that blocks the body's repair process. The way to do that, he discovered, is to immediately flush the injury site with a calcium-free salty solution that also contains methylene blue, a chemical that blocks oxidation reactions. Calcium and oxidation drive the formation of tiny spheres called vesicles, which in turn seal the nerve stumps.

The two still-unsealed stumps can then be glued together using polyethylene glycol, or PEG, which Bittner says allows the outer insulating layers of the nerve to join up more efficiently than they would through suturing.

Only when the nerve has been glued together does Bittner restart the body's natural local repair mechanism - by injecting a calcium-rich salty solution. Vesicles quickly consolidate the join (Journal of Neuroscience Research, DOI: 10.1002/jnr.23022 and 10.1002/jnr.23023).

All the substances for the procedure are already in medical use. "We are planning a small clinical trial once we have more safety data," says Thayer.

Work is also under way to see if the technique could help heal the spinal cord as well as the nerves that branch from it. Bittner says he's already shown that the new procedure works on spinal cords "in a dish", and evaluations in animals have been done too, but he is keeping these results under wraps until the work is published in a peer-reviewed journal.

Other nerve specialists are fascinated by the results, but all warn that the outcome might not be as impressive in injured humans because real-world wounds are often much more complex than those produced in the lab rats. "Clinical injuries are normally messy, not carefully controlled microlesions," says John Priestley of Queen Mary, University of London.

Giorgio Terenghi at the University of Manchester, UK, says that the technique won't work in people with injuries that are more than a few days old. Not only will the nerve stumps have sealed, but the chunk of nerve cut adrift from the rest of the nervous system begins to decay. Bittner and Thayer say they are working on ways to improve the survival time of the isolated section.

The caution greeting the new work is understandable, given that researchers are keen to avoid raising hopes prematurely. But it was also mixed with optimism. "As a beginning it's very encouraging," says Terenghi.

"It would be a major breakthrough if the severed pieces of a nerve could be just glued together - although most research indicates that this is not possible," says Priestley. "The two new papers describe something truly startling and exciting."

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