Carbohydrate mimics promote functional recovery after peripheral nerve repair

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Ann Neurol. 2006 Oct;60(4):430-7.

Carbohydrate mimics promote functional recovery after peripheral

nerve repair.

Simova O, Irintchev A, Mehanna A, Liu J, Dihne M, Bachle D, Sewald

N, Loers G, Schachner M.

Zentrum fur Molekulare Neurobiologie, Universitat Hamburg, Hamburg,

Germany.

OBJECTIVE: The outcome of peripheral nerve repair is often

unsatisfactory, and efficient therapies are not available. We tested

the therapeutic potential of functional mimics of the human natural

killer cell glycan (3-sulfoglucuronyl beta1-3 galactoside) (HNK-1)

epitope, a carbohydrate indicated to favor specificity of motor

reinnervation in mice.

METHODS: We applied a linear HNK-1 mimic peptide, scrambled peptide,

or vehicle substances in polyethylene cuffs used to reconstruct the

severed femoral nerves of adult mice. We used video-based motion

analysis and morphological and tracing techniques to monitor the

outcome of nerve repair.

RESULTS: After glycomimetic application, quadriceps muscle function

recovered to 93% of normal within 3 months. Restoration of function

was less complete (71-76%) in control groups. Better functional

recovery was associated with larger motoneuron somata, better axonal

myelination in the quadriceps nerve, and enhanced precision of

target reinnervation. Lesion-induced death of motoneurons was

reduced by 20 to 25%. The glycomimetic enhanced survival and neurite

outgrowth of both mouse and human motoneurons in vitro by 30 to 75%.

Application of a novel cyclic glycomimetic also enhanced functional

recovery in vivo.

INTERPRETATION: The improved outcome of nerve repair after

glycomimetic application may be attributed to neurotrophic effects.

Our results hold promise for therapeutic use in humans.