A WAY may have been found to overcome one of the key obstacles to repairing spinal cord injuries. The approach has already proved successful in animal tests, though by itself it is unlikely to be enough to treat spinal injuries in people. It could, however, eventually form one element of a three or four-pronged strategy.
The treatment would consist of a short course of injections to overcome the chemical signals that inhibit the regrowth of severed neurons in the spinal cord. Papers on the approach are being prepared by three separate groups of researchers.
Persuading nerves to grow again is just one of the obstacles to repairing spines, however. The neurons also have to grow through the scar tissue around an injury and make working connections, for instance.
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Nevertheless, the new work is promising. The inhibition of nerve growth in the spinal cord has been long recognised as part of the reason why people paralysed after spinal cord injuries rarely recover. Hopes of a cure for paralysis were sparked by the discovery of an inhibitory factor, NOGO, in the spinal cord, and the development of an antibody called IN-1, which binds to NOGO and blocks its effects.
But IN-1 failed to live up to its promise in some animal tests. And other research has revealed that the spinal cord contains at least two other inhibitory factors, called myelin-associated glycoprotein and oligodendrocyte myelin glycoprotein.
Two years ago, however, it was discovered that all three inhibitory factors act by binding to the same receptor on the surface of neurons, raising the possibility that blocking this receptor, or the changes it triggers inside neurons, could work instead. And this is what the latest approach seems to have achieved.
A team led by Marie Filbin at City University of New York has found that raising levels of a common signalling molecule called cyclic AMP (cAMP) overcomes the inhibitory effect of factors such as NOGO. This suggests that the receptor inhibits growth by decreasing cAMP. And there is already a drug called rolipram that raises cAMP levels.
So Filbin鈥檚 team tried giving rolipram to rats with spinal injuries. A group of 20 rats had their spinal cords severed in the neck region on one side only. After two weeks, half were given an infusion of rolipram for a further two weeks. At the end of the treatment, 70 per cent of the rolipram group could reach up with their front paws on the damaged side of their bodies, compared with just 20 per cent of the rats injected with a placebo.
鈥淭hese results suggest that increasing intraneuronal cAMP following injury enhances functional recovery,鈥� Filibin told a neuroscience meeting in New Orleans last month, where she presented some of her preliminary data. Two other groups, led by Mary Bunge at the University of Miami and Mark Tuszynski at the University of California, San Diego, are investigating similar approaches.
Encouragingly, rolipram is likely to be safe in humans, as it used to be licensed as an antidepressant. It was withdrawn because it caused nausea and vomiting in some patients, but this side effect does not occur if the drug is injected, as it would be if used to treat spinal injuries.
But the treatment of spinal injuries is a field that has seen many false dawns, and other researchers are urging caution. 鈥淣ot all findings live up to their initial promise,鈥� says Clifford Woolf of Massachusetts General Hospital in Boston.