[Novel migraine treatment with CGRP-related monoclonal antibodies]

Migraine is a common and debilitating neurological disorder characterized by recurrent attacks of moderate to severe throbbing headache accompanied by nausea, vomiting and photophobia/phonophobia. Because of its high prevalence, migraine causes a considerable financial burden on the society as well as impaired quality of life in individual patients. Scientific evidence shows that migraine is a quite complex neurological disorder that involves not only the trigeminovascular and autonomic systems but also the hypothalamus and cerebral cortex. Calcitonin gene-related peptide (CGRP) was originally discovered as a 37-amino acid neuropeptide derived from a calcitonin gene splicing variant. CGRP is found to be expressed in trigeminal ganglion neurons. Much attention has been attracted to this molecule since CGRP was found to be released from trigeminal terminals in animal migraine models. Subsequent studies demonstrated that CGRP administration induced migraine-like headache attacks specifically in migraineurs, thus highlighting a pivotal role of CGRP in the development of migraine attacks. Several CGRP receptor antagonists were shown to be efficacious for the treatment of acute migraine. Among them, telcagepant, was shown to exert a significant migraine prophylactic action as well. Nevertheless, the development of most of these agents were discontinued due to hepatotoxicity. Currently, newer CGRP receptor antagonists are being developed. On the other hand, monoclonal antibodies targeting CGRP and its receptor showed consistent efficacy for migraine prophylaxis with excellent safety profiles in Phase III clinical trials. Furthermore, emerging data support the long-term safety and efficacy of these antibodies. In this review article, the development and perspective of anti-migraine therapeutic strategies using CGRP-related antibodies are discussed.