WESTPORT, CT (Reuters Health) Apr 23 - Treatment of rats with chondroitinase ABC following experimental division of central nervous system (CNS) axons facilitates axonal regrowth to their proper targets, according to a report in the May issue of Nature Neuroscience.
"The first attempts at partial repair of spinal cord injuries are not far off," Dr. James W. Fawcett, from the University of Cambridge in the UK, told Reuters Health. "A project is already under way to design the protocols for the first spinal injury repairs in humans."
Scars containing chondroitin sulfate-bearing proteoglygans prevent axonal regeneration after CNS injury in adult mammals, Dr. Fawcett and colleagues explain in the journal. Chondroitinase ABC can degrade these compounds and should reduce the growth inhibition attributed to them.
Dr. Fawcett and his colleagues measured CNS axonal regeneration after nigrostriatal tract axotomy in untreated rats and rats that received repeated infusions of chondroitinase ABC to the injury site.
Dopaminergic axons grew through the injury site of treated rats along the course of the original nigrostriatal tract and back to their original targets, the authors report. In untreated rats, however, axons failed to regenerate beyond the axotomy site.
Immunohistochemistry results confirmed the long-distance regeneration of cut dopaminergic nigral axons in animals treated with chondroitinase ABC, but not in untreated animals. Additional studies demonstrated that chondroitinase ABC (but not penicillinase, a control protein) degraded chondroitin sulfate in the region where axonal regeneration was proceeding.
"This result," the authors conclude, "suggests that the effects of chondroitinase ABC should be evaluated in other models of CNS injury, with the long-term intention of treating human spinal cord injuries."
"The time over which this particular enzyme can be applied will be limited to a week or so, because it is a bacterial enzyme that provokes an immune response," Dr. Fawcett told Reuters Health. "This may be enough, when coupled with other treatments, to allow axons to traverse the most inhibitory parts of the glial scar."
Dr. Fawcett concluded with cautious optimism: "Repairing a cord injury to the extent that patients can walk is not at present a realistic aim for most patients. However, many patients would benefit greatly from regeneration of axons over a few centimeters, allowing them to regain breathing or movement in their hands. Like all difficult and novel treatments, the first efforts will result in small improvements."
Nat Neurosci 2001;4:465-466.
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