More MS news articles for July 2002

Peptide promotes axonal regrowth

http://neurologypdf.thelancet.com/pdfdownload?uid=lneu.1.3.newsdesk.21423.1&x=x.pdf

THE LANCET Neurology Vol 1 July 2002
Helen Frankish

US researchers have discovered a peptide that could help neurons to regenerate after CNS injury. It could be an “effective therapeutic agent in conditions characterised by failure of axonal regeneration”, such as spinal-cord injury, brain trauma, stroke, and multiple sclerosis, the investigators suggest.

“Previous work has shown that white matter of the brain contains a protein, called Nogo, that is capable of limiting axon growth through a Nogo receptor on axons”, says lead researcher Stephen Strittmatter (Yale University, New  Haven, CT, USA). A 66 amino acid residue (Nogo-66) within the molecule is responsible for preventing axonal regrowth. In the present study, Strittmatter and colleagues tested the efficacy of Nogo receptor antagonists, derived from fragments of Nogo-66, in rats with mid-thoracic spinal cord hemisection. They found that intrathecal administration of the antagonist NEP1 40 caused sig-nificant axonal sprouting and functional recovery (Nature 2002; 417: 547–51).

“Therapeutically, this might have large implications”, says Strittmatter. “However, a number of steps remain. Optimisation of the Nogo receptor antagonist and assays for toxicity must still be performed in animals before it would be appropriate to consider a clinical trial.”

Karim Fouad (University of Alberta, Canada) comments that these results are “very exciting”. However, he urged caution when speculating about the potential therapeutic effects of Nogo inhibition. “The role of Nogo in the human CNS is still unknown, and undesired side-effects of facilitated axonal sprouting and growth might occur.” Future studies using knockout or transgenic animal models, as well as long-term studies, will be essential to resolve these issues, he notes.

Fouad adds that Nogo is just one of several obstacles preventing axonal regeneration after spinal-cord injury, and it is likely that a combination of therapies could be needed to treat spinal-cord damage effectively. These might include cellular grafts to bridge the lesion site, such as Schwann cells, olfactory ensheathing cells, or stem cells; application of neurotrophic factors to enhance axonal survival and growth; and degradation of chondroitin sulphate proteoglycans with chondroitinase ABC (see The Lancet Neurology 2002; 1: 78). “Combinations with bridging techniques will definitely be required for treating severe or even anatomically complete spinal-cord injuries”, says Fouad, “since the neutralisation of Nogo by itself will not be sufficient to allow axonal growth through scar tissue and the lesion site”.