Intrathecal delivery of hepatocyte growth factor from amyotrophic lateral sclerosis onset suppresses disease progression in rat amyotrophic lateral sclerosis model

Aya Ishigaki, Masashi Aoki, Makiko Nagai, Hitoshi Warita, Shinsuke Kato, Masako Kato, Toshikazu Nakamura, Hiroshi Funakoshi, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

Hepatocyte growth factor (HGF) is one of the most potent survival-promoting factors for motor neurons. We showed that introduction of the HGF gene into neurons of G93A transgenic mice attenuates motor neuron degeneration and increases the lifespan of these mice. Currently, treatment regimens using recombinant protein are closer to clinical application than gene therapy. To examine its protective effect on motor neurons and therapeutic potential we administered human recombinant HGF (hrHGF) by continuous intrathecal delivery to G93A transgenic rats at doses of 40 or 200 μg and 200 μg at 100 days of age (the age at which pathologic changes of the spinal cord appear, but animals show no clinical weakness) and at 115 days (onset of paralysis), respectively, for 4 weeks each. Intrathecal administration of hrHGF attenuates motor neuron degeneration and prolonged the duration of the disease by 63%, even with administration from the onset of paralysis. Our results indicated the therapeutic efficacy of continuous intrathecal administration of hrHGF in transgenic rats and should lead to the consideration for further clinical trials in amyotrophic lateral sclerosis using continuous intrathecal administration of hrHGF.

Original languageEnglish
Pages (from-to)1037-1044
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume66
Issue number11
DOIs
Publication statusPublished - 2007 Nov

Keywords

  • Amyotrophic lateral sclerosis
  • Continuous intrathecal delivery
  • Hepatocyte growth factor
  • Neurodegeneration
  • Superoxide dismutase-1 (SOD1)
  • Transgenic rat

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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