Apr 10, 2002
NEW YORK (Reuters Health)
Immediate intrathecal treatment with chondroitinase ABC (ChABC) permits regrowth of axons following spinal cord injury (SCI) in rats, resulting in some restoration of function, British investigators report in the April 11th issue of Nature.
Dr. Elizabeth J. Bradbury, of King's College London, and colleagues caused cervical (C4) dorsal column crush lesions in adult rates, and then infused protease-free ChABC or a control solution. Functional connections were demonstrated by the evocation of postsynaptic cord dorsum potentials below the lesion, averaging about 40% of that evoked by stimulation at C3, and significantly more than that in control SCI animals treated with vehicle (p < 0.001).
Behavioral testing showed significant improvement in walking beginning 1 week after injury and treatment. By 6 weeks, foot slips when crossing a narrow beam or grid were not significantly different from sham controls (p > 0.1). Also, ChABC prevented most changes in stride length and width that were observed in SCI rats treated with control solution. However, sensory function remained impaired, as illustrated by a lack of ability to sense and remove adhesive tape applied to the forepaw.
Other evidence of a regenerative state included upregulation of growth-associated protein 43 in large diameter neurons, from 6% in control-treated animals to 22% in ChABC-treated animals. Electron microscopy showed that nerve fiber retraction that occurred in control-treated SCI was prevented by ChABC, with some axons regrowing through and beyond the lesion area, with evidence of growth-cone-like endings.
Chondroitinase ABC joins "NogoA, neurotrophic factor treatment, gene therapy and cellular grafting as interventions that promote spinal cord regeneration," Dr. Bradbury and her associates conclude.
In a commentary, Dr. Lars Olson, of the Karolinska Institute in Stockholm, noted that purified ChABC exerts no protein-degrading activity, so is likely to be safe in humans. However, he added, it is possible that the enzyme could degrade chondroitin sulfate proteoglycans present in gray matter.
Dr. Olson also notes that in experimental models, no technique has led to complete recovery. He suggests that combinations of treatments may improve the prognosis of patients with SCI.
Nature 2002;416:589-590, 636-640.
© 2002 Reuters Ltd