Antibodies and methods for wnt pathway related diseases

Abstract

The transmembrane E3 ubiquitin ligases ZNRF3 and RNF43 are negative regulators of β-catenin and Wnt signaling pathways in eukaryotic cells. Antibodies that bind to the extracellular domain of ZNRF3 can modulate the activity of ZNRF3, resulting in enhanced Wnt signaling. ZNRF3 antagonistic antibodies can be used to treat diseases with weak Wnt signaling, such as short bowel syndrome, osteoporosis, diabetes, neurodegenerative diseases and mucositis. Furthermore, the antagonistic antibodies of the present invention can be used to enhance Wnt signaling for tissue repair and wound healing.

Description

technical field [0001] The present invention relates broadly to monoclonal antibodies that bind to receptors, and more particularly to antibodies that bind to ZNRF3 protein or RNF43 protein. Background technique [0002] The Wnt signaling pathway is a protein network in eukaryotic cells that is important for regulating cell growth and differentiation. LoganCY and Nusse R, "The Wnt signaling pathway in development and disease." Annu. Rev. Cell. Dev. Biol. 20:781-810 (2004); Nusse R., "Wnt signaling in disease and in development." Cell Res .15(1):28-32 (January 2005); Clevers H, "Wnt / beta-catenin signaling in development and disease." Cell 127(3):469-80 (3Nov.2006). Wnt signaling is critical for regulating cell growth and differentiation during embryonic development. In adults, Wnt signaling promotes tissue homeostasis. [0003] Dysregulation of Wnt signaling has been linked to many human diseases. Abnormal overactivation of the Wnt pathway may be involved in the oncogenes...

AI Technical Summary

Problems solved by technology

[0008] Although many proteins are involved in the Wnt signaling pathway, few proteins have been identified as druggable targets in this pathway, especially those upstream in the β-catenin pathway in the Wnt pathway

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