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The secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1) is a multifunctional pathogenic signalling molecule which, amongst other activities, modulates the TGFβ pathway in a highly context-dependent manner. LRG1 was first described as a key player in pathogenic ocular neovascularization a decade ago. Since then, an increasing number of publications have reported the involvement of LRG1 in multiple human conditions including cancer, diabetes, cardiovascular disease, neurological disease, and inflammatory disorders. Effective blocking of LRG1 therefore offers platform therapeutic value across many disease indications.


Continued LRG1 presence leads to disease

LRG1 acts as an effective “acute phase” protein that contributes to the innate immune response. Although almost absent in healthy individuals, inflammation and infection trigger expression of LRG1. As a component of the repair mechanism it induces de-differentiation of epithelial, endothelial and pericyte cells enabling cell survival, proliferation, immune cell infiltration, vessel restoration and wound healing.

Upon restoration of homeostasis, LRG1 is switched off. However, under chronically stressed cell conditions, LRG1 continues to be expressed and has aberrant effects: Fibrosis, loss of vascular integrity and cancer cell proliferation and migration.


Main pathogenic mechanism of LRG1

Under chronic conditions LRG1 drives excessive and uncontrolled signalling of the TGFβ cascade. LRG1 binds to TGFβ receptors switching TGFβ cascade from homeostatic to pathogenic motif.

Senya’s Pipeline

Senya Therapeutics is developing proprietary biologics targeting LRG1 to provide therapeutic interventions in these key disease populations. To date, the company has developed a lead molecule, STX-002, that inhibits the activity of LRG1 and has successfully demonstrated its efficacy in a range of translational preclinical models. These results have shown that the compound is safe and well-tolerated, and that these approaches can be used to treat disease through vascular normalisation, deceleration of fibrosis, and an improved microenvironment.

In addition to STX-002, Senya is developing STX-001, a fragment of STX-002, intended for ophthalmology indications.


General LRG1 Review