Antibody Blocks GDF15 Pathway to Ease Cachexia in Mice

Researchers have developed an antibody designed to interrupt a signaling pathway tied to the severe weight and muscle loss seen in cancer cachexia, according to a study published in Science Advances.

The target is GFRAL, a receptor found in the hindbrain that responds to GDF15, a stress related cytokine. When this receptor pathway becomes overactive, it can drive the body into a wasting state, contributing to the profound weight loss many cancer patients experience. The team created an antibody called GB2Ab that binds GFRAL and blocks it from forming a complex with GDF15 and a related kinase, RET. Structural analysis showed the antibody uses what the authors describe as an induced fit mechanism, reshaping the usual binding site and producing a tight, slow releasing grip on the receptor.

In an orthotopic mouse model of cancer cachexia, a humanized version of the antibody reached the brainstem area involved in this signaling, reduced GDF15 driven nerve activation, eased cachexia symptoms, and lowered overactive sympathetic nervous system signaling.

This is early stage animal research, not a human trial, and the antibody is not an approved treatment. The findings point to GFRAL blockade as one possible research direction for cachexia linked to cancer and other GDF15 driven conditions, but much work remains before any clinical use could be considered.

This article is for education only. It is not medical advice. Compounds discussed here are sold for research purposes. Talk to a licensed clinician before making health decisions.