Miércoles 15 de Febrero de 2006, Ip nº 140

'Walk again' drugs to be tested on people
Por Prashant Nair

TWO antibodies that enabled the severed spinal nerves of rats to be regenerated are to be tested in humans.

The antibodies have helped rats with damaged spinal cords to walk again, by blocking the action of Nogo, a protein that stops nerve cells sprouting new connections. But there were concerns about whether blocking Nogo would lead to uncontrolled neuronal rewiring in the brain or spinal cord and it was also unclear how such a therapy could be given to humans.

Now Martin Schwab and his colleagues at the University of Zurich in Switzerland have infused two antibodies, 11C7 and 7B12, into the damaged spinal cords of rats. An osmotic mini-pump connected to a fine catheter was used to deliver the antibodies directly into the cerebrospinal fluid surrounding the injured part of the spinal cord - a method of delivery that could easily be applied to humans, they say. The antibodies triggered regeneration of axons, the fine thread-like extensions that connect neurons, and enabled injured rats to swim, cross the rungs of a ladder without slipping and traverse a narrow beam (Annals of Neurology, vol 58, p 706).

Moreover, the antibodies did not cause hyperalgesia, a condition in which even a simple touch is sensed as pain - a sign that would have indicated wrong neuronal connections had been made.

Schwab's team has been developing antibodies that are suitable for humans in collaboration with pharmaceutical giant Novartis. He says they intend to begin clinical trials lasting two to three years in the very near future.

"There is sufficient experimental evidence to view these trials with some optimism," says Robin Franklin, a neuroscientist at the University of Cambridge.

But blocking Nogo alone might not lead to complete recovery, says team member Lisa Schnell. More likely, it could become part of a combined approach to treating spinal injuries. "What we still need is a bridge that links the lesioned nerve to the rest of the spinal cord," she says. The nerves also need growth factors in order to keep sprouting and stay functional.

Towards this end, Geoffrey Raisman at University College London is working on supplying the necessary stimulants for nerve regrowth by transplanting sheath cells from the back of the nose onto the spinal cord of patients. These cells are renowned for their ability to foster regeneration of injured nerve fibres. Such treatments have shown promise in paralysed dogs, which regained some movement in their legs after the transplant (New Scientist, 16 April 2005, p 14). Clinical trials in humans are expected to begin this year.

Nick Jeffery, a veterinary surgeon at the University of Cambridge who carried out the experiments in dogs, cautions against translating the results of animal experiments directly into humans. While there is reason to be optimistic about the prospects of using antibodies to block Nogo, there could be differences in the extent of functional recovery between rats and humans, he says. Blocking Nogo in humans could also have other, as yet unknown, effects on the body.

  11/02/2006. New Scientist Magazine.