Clinical application and potential pluripotent effects of hepatocyte growth factor in spinal cord injury regeneration

ABSTRACT

Introduction

Spinal cord injury (SCI) is a condition in which the spinal cord parenchyma is damaged by various factors. The mammalian central nervous system has been considered unable to regenerate once damaged, but recent progress in basic research has gradually revealed that injured neural cells can indeed regenerate. Drug therapy using novel agents is being actively investigated as a new treatment for SCI. One notable treatment method is regeneration therapy using hepatocyte growth factors (HGF).

Area covered

HGF has pluripotent neuroregenerative actions, as indicated by its neuroprotective and regenerative effects on the microenvironment and damaged cells, respectively. This review examines these effects in various phases of SCI, from basic research to clinical studies, and the application of this treatment to other diseases.

Expert opinion

In regenerative medicine for SCI, drug therapies have tended to be more likely to be developed compared to cell replacement treatment. Nevertheless, there are still challenges to be addressed for these clinical applications due to a wide variety of pathology and animal experimental models of basic study, but HGF could be an effective treatment for SCI with expanded application.

KEYWORDS:

• Clinical application
• clinical trial
• drug therapy
• hepatocyte growth factor
• neuroprotective factor
• regenerative medicine
• spinal cord injury

Article highlights

• Spinal cord injury (SCI) is a condition in which the spinal cord parenchyma is damaged by various factors.

• Recent remarkable progress in basic research has revealed that injured mammalian central nervous systems can regenerate.

• Hepatocyte growth factor (HGF) has pluripotent neuroregenerative actions such as its neuroprotective and regenerative effects on the microenvironment and damaged cells, respectively.

• A phase I/II clinical trial of HGF therapy for acute SCI has been completed and is suggested to contribute to motor function recovery.

• HGF has been indicated in basic research for various phases of injury as well as in acute SCI.

• HGF is expected to be effective against diseases other than SCI and many clinical trials are underway worldwide.

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13543784.2024.2360191

Declaration of interests

H Okano declared employment with Keio University School of Medicine, advisory role with SanBio Co. Ltd., and K Pharma, Inc., and research funding from SanBio Co. Ltd., and K Pharma, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conceptualization, S Hashimoto, N Nagoshi, M Nakamura, and H Okano.; Writing – Original Draft, S Hashimoto and N Nagoshi; Editing, M Nakamura and H Okano; Supervision, S Hashimoto, N Nagoshi, M Nakamura and H Okano; Funding Acquisition, S Hashimoto, N Nagoshi, M Nakamura and H Okano All authors read and approved the final manuscript.

Additional information

Funding

This work was supported by the following grants: Research Center Network for Realization of Regenerative Medicine by AMED Japan ((grant Nos. JP22bk0104114, JP21bm0204001, JP20bk0104017, JP24ym0126118, and 24bm1223008) to H.O., M.N., and N.N.) and the Japan Society for the Promotion of Science (JSPS) (KAKENHI grant number 22H03205 to N.N.). This manuscript was also funded by Kringle Pharma, Inc. (Osaka, Japan).