01 June 2002
Volume 1, Number 2
A bacterial enzyme could offer new hope for patients with spinal cord injuries, say UK researchers. Elizabeth Bradbury (King's College London, UK) and colleagues saw “very clear functional recovery” after injecting chrondroitinase ABC intrathecally at the injury site in rats with crush injuries of the cervical dorsal column (Nature 2001; 416: 636–40).
Chondroitinase ABC works by degrading chondroitin sulphate proteoglycans (CSPGs) formed in glial scar tissue at the injury site. “CSPGs block the growth of regenerating axons, and this inhibitory activity can be attenuated by removing the molecule's glycosaminoglycan side chain with chondroitinase ABC”, Bradbury explains. In injured rats, chondroitinase ABC promoted functional recovery and regeneration of both ascending and descending pathways. Walking was restored to near-normal in treated rats, indicating recovery of both locomotor function and proprioception. But sensorimotor function (awareness and removal of adhesive tape on the forelimbs) did not recover significantly, suggesting that chondroitinase ABC did not promote regeneration of hindbrain sensory nuclei. Chondroitinase ABC also upregulated expression of a nerve-regeneration marker protein, growth-associated protein 43. In anaesthetised animals electrical stimulation of the motor cortex evoked large, though delayed, postsynaptic potentials below the lesion site. The authors suggest that “chondroitinase ABC and other potential treatments that affect CSPG production after injury may have therapeutic potential for the treatment of patients with spinal cord injuries”.
These experiments are “exceptional in that they combine anatomical, physiological, and behavioural evidence for functional regeneration after spinal cord injury”, says Patrick Anderson (University College London, UK). “It is widely believed that both inhibitory molecules such as CSPGs and the poor regenerative response of many CNS neurons contribute to the failure of axonal regeneration after spinal cord injury”, he adds. “Curiously, chondroitinase appears to remove inhibitory influences and enhance the intrinsic regenerative response of the injured cells.” Anderson points out that “major problems for patients arise when segments of the cord are completely, or almost completely destroyed”, by contrast to the lesions in the rat experiments. “It is not known yet whether chondroitinase treatment will be effective on much larger lesions.”
Anderson notes that other experimental treatments, including vaccination with CNS myelin and treatment with specific antibodies to the nerve-growth inhibitory protein Nogo, have produced axonal regeneration in the spinal cord. “The major significance of all these studies is not that they necessarily offer the immediate prospect of successful treatments for patients but that they offer exciting opportunities to find out what normally prevents axons from regenerating in the CNS.”