Clinical translation of hepatocyte growth factor for amyotrophic lateral sclerosis

Hitoshi Warita, Masaaki Kato, Naoki Suzuki, Yasuto Itoyama, Masashi Aoki

Research output: Contribution to journalArticlepeer-review


Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons. Approximately 20% of familial ALS cases are linked to mutations in Cu/Zn superoxide dismutase (SOD1) gene. Previously, we developed a transgenic rat model of ALS overexpressing mutant SOD1 protein. The rat model facilitates preclinical ALS research employing various therapeutic approaches such as intrathecal administration, cell transplantation, and viral vector-mediated gene transduction to the affected central nervous system. Hepatocyte growth factor (HGF) is a pleiotropic growth factor and also a potent survival-promoting factor for motor neurons. To examine its therapeutic effect on ALS, we administered human recombinant HGF (hrHGF) to the transgenic ALS rats. In contrast with vehicle-treated rats, continuous intrathecal infusion of hrHGF attenuated spinal motor neuron degeneration and prolonged the duration of the disease, even with administration from the onset of symptoms. To translate the strategy to human treatment, we performed dose-finding and safety studies using nonhuman primate model of contusive cervical spinal cord injury. Introducing exogenous HGF protein also revealed a distinct therapeutic effect with functional recovery. Given the therapeutic potential of hrHGF on ALS, we started a novel phase I clinical trial for ALS patients in Tohoku University Hospital.

Original languageEnglish
Pages (from-to)1214-1217
Number of pages4
JournalClinical Neurology
Issue number11
Publication statusPublished - 2012 Dec 1


  • Amyotrophic lateral sclerosis
  • Hepatocyte growth factor
  • Intrathecal administration
  • SOD1
  • Transgenic rat

ASJC Scopus subject areas

  • Clinical Neurology


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