title: Glycomimetic improves recovery after femoral injury in a non-human primate.
abstract: In adult mammals, restoration of function after peripheral nerve injury is often poor and effective therapies are not available. Previously we have shown in mice that a peptide which functionally mimics the human natural killer cell (HNK)-1 trisaccharide epitope significantly improves the outcome of femoral nerve injury. Here we evaluated the translational potential of this treatment using primates. We applied a linear HNK-1 mimetic or a functionally inactive control peptide in silicone cuffs used to reconstruct the cut femoral nerves of adult cynomolgus monkeys (Macaca fascicularis). Functional recovery was evaluated using video-based gait analysis over a 160-day observation period. The final outcome was further assessed using force measurements, H-reflex recordings, nerve histology, and ELISA to assess immunoreactivity to HNK-1 in the treated monkeys. Gait deficits were significantly reduced in HNK-1 mimetic-treated compared with control peptide-treated animals between 60 and 160 days after injury. Better outcome at 160 days after surgery in treated versus control animals was also confirmed by improved quadriceps muscle force, enhanced H-reflex amplitude, decreased H-reflex latency, and larger diameters of regenerated axons. No adverse reactions to the mimetic, in particular immune responses resulting in antibodies against the HNK-1 mimetic or immune cell infiltration into the damaged nerve, were observed. These results indicate the potential of the HNK-1 mimetic as an efficient, feasible, and safe adjunct treatment for nerve injuries requiring surgical repair in clinical settings.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, Hamburg, Germany. andrey.irintchev@med.uni-jena.de
authors.forename: Andrey
authors.initials: A
authors.lastname: Irintchev
authors.forename: Ming-Mei
authors.initials: MM
authors.lastname: Wu
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Feng
authors.forename: Yan-Sheng
authors.initials: YS
authors.lastname: Liu
authors.forename: Christian
authors.initials: C
authors.lastname: Bernreuther
authors.forename: Gabriele
authors.initials: G
authors.lastname: Loers
authors.forename: Si-Wei
authors.initials: SW
authors.lastname: You
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005240:Feasibility Studies; D020428:Femoral Neuropathy / Q000188:drug therapy* / Q000503:physiopathology; D008252:Macaca fascicularis; D008297:Male; D018716:Molecular Mimicry / Q000502:physiology*; D010456:Peptides, Cyclic / Q000502:physiology / Q000627:therapeutic use; D011134:Polysaccharides / Q000819:agonists / Q000502:physiology / Q000627:therapeutic use*; D055630:Receptors, NK Cell Lectin-Like / Q000819:agonists / Q000502:physiology / Q000627:therapeutic use*; D020127:Recovery of Function; D014312:Trisaccharides / Q000819:agonists / Q000502:physiology / Q000627:therapeutic use*
chemical_list: D010456:Peptides, Cyclic; D011134:Polysaccharides; D055630:Receptors, NK Cell Lectin-Like; D014312:Trisaccharides