Endocrine / Metabolic

Mouse studies suggest inhibiting CGRP-expressing neurons could help treat cancer-associated anorexia and malaise. In a mouse model of the indication, levels of the neuronal activation marker c-fos were higher in CGRP-expressing parabrachial nucleus neurons than in neurons from normal mice. Also in the model, injection of an adenoviral vector targeting CGRP-expressing parabrachial nucleus neurons and encoding tetanus toxin -- an inhibitor of neural activation -- into the parabrachial nucleus decreased lethargy, anxiety-like behaviors, hunched posture and other markers of malaise, and weight loss and increased food intake compared with empty vector. Also in the model, systemic administration of a tool compound that inhibits the activation of CGRP-expressing parabrachial nucleus neurons decreased weight loss and increased food intake compared with vehicle. In a mouse model of intestinal cancer-associated weight loss, injection of the toxin-encoding adenoviral vector into the parabrachial nucleus decreased weight loss and increased food intake compared with empty vector. Next steps include identifying and testing inhibitors of CGRP-expressing parabrachial nucleus neurons in models of cancer- and non-cancer-associated anorexia and malaise.

Eli Lilly and Co. has galcanezumab (LY2951742), a humanized mAb targeting CGRP, in Phase III testing to prevent chronic migraine, cluster headaches and episodic migraine...