Gal-8 Inhibition as a Treatment of Diseases associated with pathological Lymphangiogenesis
Targeting Galectin-8 to prevent lymphangiogenesis
Lead Inventor: Dr. Noorjahan Panjwani
Tufts case T001991
Bussiness Opportunity: Researchers at Tufts University have shown that Galectin-8 inhibitors prevent lymphangiogenesis (LA) in a relevant animal model. There is now an opportunity to exploit these scientific discoveries to develop improved therapeutics for diverse pathologies that are associated with aberrant LA.
Overview: LA is the formation of new lymphatic vessels from pre-existing lymphatic vessels. This process is associated with a variety of pathologies, including but not limited to, metastatic dissemination, graft rejection, chronic inflammation and lymphedema. A key mediator of LA is the tyrosine kinase receptor VEGFR-3, which binds to the ligand VEGF-C. Another transmembrane receptor, Podoplanin (PDPN), has also been implicated in LA, however, a mechianistic understanding of its role in promoting LA has remained unclear. Recently, Dr. Panjwani and her colleagues at Tufts University have discovered that Galectin-8, a member of a family of galactoside-binding lectins, is a key mediator of LA. They demonstrated that injection of Galectin-8 into mouse corneas can promote LA in a dose dependant manner in vivo and that this activity of Galectin-8 is carbohydrate-specific. Furthermore, they demonstrated that Galectin-8 and PDPN are both required for VEGF-C mediated LA in primary-derived lymphatic endothelial cell (LEC) spheroids in vitro. The mechanism for this is likely through Galectin-8 mediated cross-linking of VEGFR-3 and PDPN via glycans attached to these surface proteins on LECs. This results in signaling through AKT and ERK pathways, which promotes LA. Importantly, these Tufts researchers also demonstrated that inhibiting Galectin-8 prevents LA in vivo using thiodigalactoside (a pan inhibitor of galectins) and Gal-8N (a dominant-negative inhibitor of Galectin-8). Thus, Tufts researchers have now uncovered that Galectin-8 represents a novel therapeutic target for preventing LA.
Applications: These findings strongly support the prospect for Galectin-8 inhibitors as a therapeutic intervention for preventing LA. Aberrant LA is associated with lymphedema, graft rejection, tumor metastasis, and chronic inflammation.
Opportunity: This technology is available for licensing and sponsored research.
Intellectual Property: US Patent No. 10,226,509 (March 12, 2019)