A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord

Shinjiro Kaneko, Akio Iwanami, Masaya Nakamura, Akiyoshi Kishino, Kaoru Kikuchi, Shinsuke Shibata, Hirotaka J. Okano, Takeshi Ikegami, Ayako Moriya, Osamu Konishi, Chikao Nakayama, Kazuo Kumagai, Toru Kimura, Yasufumi Sato, Yoshio Goshima, Masahiko Taniguchi, Mamoru Ito, Zhigang He, Yoshiaki Toyama, Hideyuki Okano

Research output: Contribution to journalArticle

283 Citations (Scopus)

Abstract

Axons in the adult mammalian central nervous system (CNS) exhibit little regeneration after injury. It has been suggested that several axonal growth inhibitors prevent CNS axonal regeneration. Recent research has demonstrated that semaphorin3A (Sema3A) is one of the major inhibitors of axonal regeneration. We identified a strong and selective inhibitor of Sema3A, SM-216289, from the fermentation broth of a fungal strain. To examine the effect of SM-216289 in vivo, we transected the spinal cord of adult rats and administered SM-216289 into the lesion site for 4 weeks. Rats treated with SM-216289 showed substantially enhanced regeneration and/or preservation of injured axons, robust Schwann cell-mediated myelination and axonal regeneration in the lesion site, appreciable decreases in apoptotic cell number and marked enhancement of angiogenesis, resulting in considerably better functional recovery. Thus, Sema3A is essential for the inhibition of axonal regeneration and other regenerative responses after spinal cord injury (SCI). These results support the possibility of using Sema3A inhibitors in the treatment of human SCI.

Original languageEnglish
Pages (from-to)1380-1389
Number of pages10
JournalNature medicine
Volume12
Issue number12
DOIs
Publication statusPublished - 2006 Dec

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kaneko, S., Iwanami, A., Nakamura, M., Kishino, A., Kikuchi, K., Shibata, S., Okano, H. J., Ikegami, T., Moriya, A., Konishi, O., Nakayama, C., Kumagai, K., Kimura, T., Sato, Y., Goshima, Y., Taniguchi, M., Ito, M., He, Z., Toyama, Y., & Okano, H. (2006). A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nature medicine, 12(12), 1380-1389. https://doi.org/10.1038/nm1505