
Migraine is an intense, throbbing headache that often affects one side of the head and may be accompanied by neurological symptoms, such as disturbed vision or, more rarely, speech problems. Patients with recurrent or chronic migraine may experience these headaches two or more times per week and they result in significant disability. In the 2015 Global Burden of Disease Study, migraine was the seventh-leading cause of disability worldwide and the leading neurological cause of disability, accounting for over half of the years lost to disability from all neurological disorders.
A class of drugs called triptans, which block a specific serotonin receptor, are effective for the treatment of migraine attacks. They help 40-50% of patients with this condition and are the medications prescribed most often for treatment of migraine. However, the goal for people with frequent migraines is to prevent these headaches before they occur; and, despite many years of effort, no drugs have been developed specifically for protection (prophylaxis) against migraine. Some medicines have been “repurposed” for migraine prevention. The most commonly used are beta-blockers, a class of drugs initially developed for the treatment of high blood pressure.
Calcitonin gene-related peptide (GGRP) is a small molecule with a wide range of effects that are believed to contribute to the development of migraine headaches. CGRP is present in sensory neurons involved in the transmission of signals related to pain and it is also found in vascular smooth muscle. An important clue regarding involvement of CGRP is migraine is the fact that one important action of triptans used to treat migraine attacks is that they block the release of CGRP from sensory neurons. Other studies have shown that injection of CGRP into people with a history of migraine (migraineurs) resulted in the occurrence of migraine-like headaches. These results suggested that CGRP might be an excellent target for migraine prevention and this has turned out to be the case.
Several monoclonal antibodies that bind to CGRP and block its actions are now in late-stage development for migraine prevention. Three have completed phase II studies one has finished phase III trials; and every one of these studies has provided highly positive results. In addition, no important safety issues have arisen to date. In addition, it appears that the CGRP antibodies act more quickly than current preventive options, which typically require up to 8 weeks of treatment.
So, it has been a long time coming, but a new class of drugs targeting CGRP may be the first preventative treatment specifically developed for migraine to reach prescribers and patients.
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