๐ค Authors: Alessandra Pistolesi, Simone Tuniz, Cristina Luceri, Alice Molli, Matteo Urru, Antonino Iurato La Rocca, Michele Tanturli, Francesco De Cesaris, Daniela Buonvicino, Alberto Chiarugi
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 (elPB CGRP) 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 elPB CGRP 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.
