Targeting the divergent TGFβ superfamily cytokine MIC-1/GDF15 for therapy of anorexia/cachexia syndromes.

PURPOSE OF REVIEW: To review recent finding on MIC-1/GDF15 and re-evaluate it as a potential target for the therapy of anorexia/cachexia syndromes.

RECENT FINDINGS: MIC-1/GDF15 consistently induces anorexia/cachexia in animal models. Its actions on brainstem feeding centers leads to anorexia, inducing prolonged undernutrition and consequent loss of both lean and fat mass. Epidemiological studies by multiple groups have linked substantially elevated serum levels of this cytokine to anorexia/cachexia syndromes in diverse diseases such as cancer, chronic renal and cardiac failure, and chronic obstructive lung disease. These elevated serum levels are similar to those required to induce this syndrome in animals. Recent identifications of its previously elusive receptor as GFRAL, has enhanced understanding of its biology and suggests that modulating the MIC-1/GDF15-GFRAL pathway may be a therapeutic target for anorexia/cachexia syndrome.

SUMMARY: Inhibiting MIC-1/GDF15 or its receptor GFRAL are high-value potential targets for treatment of anorexia/cachexia syndrome in patients whose elevated serum levels may justify its use.