Tissue fibrosis is a severely debilitating disease leading to excessive tissue scarring, organ injury, function decline, and even failure. Core features of organ fibrosis include epithelial and endothelial injury; abnormal proliferation of myofibroblasts, smooth muscle, and stellate cells, and failure of extracellular matrix deposition. The NASH and the resultant liver fibrosis are major health problems in the United States and the rest of the world. Currently, there are no FDA-approved medical therapies for NASH or NASH-mediated fibrosis.
Accumulating evidence suggests that galectin-3 is involved in fibrogenesis of various organs such as the liver, lung, skin, kidney, and heart (see Figure 4). During tissue fibrosis, Galectin-3 promotes pro-fibrotic factor release, activation of inflammatory cells (macrophages and others), the proliferation of extracellular matrix-producing cells (fibroblasts and myofibroblasts), and tissue injury in different organs. It is believed that galectin-3 cross-links with glycans of the TGF-β receptor resulting in prolonged activation of the receptor. Overall, data suggest that the specific inhibition of galectin-3 may represent a promising therapeutic strategy against tissue fibrosis.
Our drug GM101 has demonstrated preclinical efficacy in relevant animal models of human NASH.
Figure 4. Role of Galectin-3 in the Promotion of Organ Fibrosis
- Henderson NC, Mackinnon AC et al: Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci U S A. 2006, 103:5060-5. [PubMed]
- Mackinnon AC, Gibbons MA et al: Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3. Am J Respir Crit Care Med. 2012, 185:537-46. [PubMed]