Application of hepatocyte growth factor for acute spinal cord injury

The road from basic studies to human treatment

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2 Citations (Scopus)

Abstract

Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.

Original languageEnglish
Article number1054
JournalInternational journal of molecular sciences
Volume20
Issue number5
DOIs
Publication statusPublished - 2019 Mar 1

Fingerprint

spinal cord injuries
Hepatocyte Growth Factor
Spinal Cord Injuries
roads
Rats
Proto-Oncogene Proteins c-met
Therapeutics
Callithrix
Phase II Clinical Trials
Clinical Trials, Phase I
rats
Oligodendroglia
Nerve Growth Factors
Mitogens
Neuroglia
Astrocytes
Primates
Neurology
Cicatrix
primates

Keywords

  • Clinical trial
  • Hepatocyte growth factor
  • Recombinant human hepatocyte growth factor
  • Spinal cord injury

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

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title = "Application of hepatocyte growth factor for acute spinal cord injury: The road from basic studies to human treatment",
abstract = "Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.",
keywords = "Clinical trial, Hepatocyte growth factor, Recombinant human hepatocyte growth factor, Spinal cord injury",
author = "Kazuya Kitamura and Narihito Nagoshi and Osahiko Tsuji and Morio Matsumoto and Hideyuki Okano and Masaya Nakamura",
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T1 - Application of hepatocyte growth factor for acute spinal cord injury

T2 - The road from basic studies to human treatment

AU - Kitamura, Kazuya

AU - Nagoshi, Narihito

AU - Tsuji, Osahiko

AU - Matsumoto, Morio

AU - Okano, Hideyuki

AU - Nakamura, Masaya

PY - 2019/3/1

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N2 - Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.

AB - Hepatocyte growth factor (HGF) was first identified as a potent mitogen for mature hepatocytes, and has also gained attention as a strong neurotrophic factor in the central nervous system. We found that during the acute phase of spinal cord injury (SCI) in rats, c-Met, the specific receptor for HGF, increases sharply, while the endogenous HGF up-regulation is relatively weak. Introducing exogenous HGF into the spinal cord by injecting an HGF-expressing viral vector significantly increased the neuron and oligodendrocyte survival, angiogenesis, and axonal regeneration, to reduce the area of damage and to promote functional recovery in rats after SCI. Other recent studies in rodents have shown that exogenously administered HGF during the acute phase of SCI reduces astrocyte activation to decrease glial scar formation, and exerts anti-inflammatory effects to reduce leukocyte infiltration. We also reported that the intrathecal infusion of recombinant human HGF (intrathecal rhHGF) improves neurological hand function after cervical contusive SCI in the common marmoset, a non-human primate. Based on these collective results, we conducted a phase I/II clinical trial of intrathecal rhHGF for patients with acute cervical SCI who showed a modified Frankel grade of A/B1/B2 72 h after injury onset, from June 2014 to May 2018.

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