Anti-CGRP monoclonal antibodies counteract establishment of food aversive memories and chemotherapy-induced anorexia and weight loss

Glutamatergic neurons of external lateral parabrachial nucleus co-expressing calcitonin gene related peptide (elPBCGRP) negatively regulate food intake and establish food aversive memories. They also promote malaise-dependent anorexia, sickness behavior and tumor cachexia. In spite of the pathogenetic potential of elPBCGRP neurons in numerous human disorders, whether they can be targeted with drugs inhibiting CGRP-dependent neuromodulation remains unknown. We report that systemically administered anti-CGRP mAbs recently approved for migraine prevention reach the rat brain and counteract CGRP-regulated food aversive memories as well as chemotherapy-induced anorexia and weight loss. Anti-CGRP antibodies also partially reduce fear responses, but are unable to prevent anorexia by the GLP-1 agonist liraglutide. Data disclose the therapeutic potential of anti-CGRP monoclonals to treatment of eating disorders, including tumor treatment-associated syndromes such as chemotherapy induced nausea and vomiting or cachexia.