Review of galectin-3 inhibitors in the treatment of nonalcoholic steatohepatitis

ABSTRACT

Introduction

Galectin-3 (Gal-3) is a β-galactoside binding protein associated with many disease pathologies, including chronic inflammation and fibrogenesis. It has been implicated in the disease severity of NASH, although its precise role is unknown. Inhibition of Gal-3 has shown to improve and prevent fibrosis progression and has now reached phase III clinical trial in NASH patients.

Areas covered

This discusses the role of Gal-3 in NASH. It brings together the current findings of Gal-3 in NASH and hepatic fibrosis by analyzing recent data from animal model studies and clinical trials.

Expert opinion

Gal-3 inhibitors, in particular, Belapectin (GR-MD-02), have shown promising results for NASH with advanced fibrosis. In a phase 2 trial, Belapectin did not meet the primary endpoint. However, a sub-analysis of Belapectin among a separate group of patients without esophageal varices showed 2 mg/kg of GR-MD-02 reduced HVPG and the development of new varices. A subsequent study is under way, aiming to replicate the positive findings in phase 2 and demonstrate greater efficacy. If Belapectin is shown to be effective, it will be coupled with other drugs that target steatohepatitis to maximize efficacy and disease reversal.

KEYWORDS:

• fibrosis
• nafld
• inflammation
• liver stiffness
• Fibrosis

Article Highlights

• Galectin can be found in various organs and is present in fibroblasts, myeloid, endothelial, and epithelial cells.

• Galectin has been associated with cell growth, proliferation, differentiation, inflammation, and immune response.

• Gal-3 has an anti-apoptotic function

• Gal-3 expression was upregulated in humans with liver fibrosis.

• Despite the advances in antifibrotic therapy, most compounds are still in clinical trials and no drug is currently approved for treating NASH and advanced fibrosis.

• Gal-3 highlights its potential of being a biomarker and therapeutic target

Declaration of interest

M. Noureddin has declared being on the advisory board for Gilead, Intercept, Pfizer, Novartis, Allergan, Blade, EchoSens, Fractyl, Terns, OWL, Siemens, Roche diagnostic, and Abbott; they have also declared receiving research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Shire, Viking, and Zydus; M. Noureddin is also a minor shareholder or has stocks in Anaetos and Viking. 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.

Additional information

Funding

This paper was not funded.