Lysyl oxidase-like 1 (LOXL1) is a copper-dependent enzyme belonging to the lysyl oxidase family, which plays a critical role in extracellular matrix (ECM) remodeling by catalyzing the cross-linking of collagen and elastin. Dysregulation of LOXL1 has been implicated in fibrotic diseases, cancer progression, and metastasis, making it a potential therapeutic target. LOXL1 antibodies are designed to specifically inhibit its enzymatic activity or block its interaction with ECM components, thereby attenuating pathological tissue stiffening, tumor invasion, and fibrosis.
Research on LOXL1 antibodies gained momentum due to its association with exfoliation syndrome (XFS), a major risk factor for glaucoma. Genetic variants in LOXL1 are strongly linked to XFS, though disease mechanisms remain unclear. In oncology, LOXL1 overexpression correlates with poor prognosis in cancers like breast and colorectal, driving interest in antibody-based therapies. Early-stage clinical trials explored anti-LOXL1 agents (e.g., simtuzumab) for fibrosis and cancer, but efficacy was limited, highlighting challenges in target validation and patient stratification.
Current efforts focus on optimizing antibody specificity, understanding LOXL1's dual roles in homeostasis vs. disease, and identifying biomarkers for targeted therapy. Despite setbacks, LOXL1 remains a compelling target due to its central role in ECM pathology.