Calcitonin Gene‐Related Peptide Targeted Therapy for Migraine

WHAT ARE CGRP BLOCKING MEDICATIONS? There is an exciting new class of medications for migraine targeting the calcitonin gene-related peptide (CGRP). Peptides are chains of amino acids which are shorter than proteins. They have been described as small proteins. CGRP blocking medications are likely to become available in the next several years. None of these medications are approved by the Food and Drug Administration (FDA) at the time of this writing. These drugs appear to be highly effective and specific medications designed to either prevent or acutely treat migraines through blocking the pain pathway most likely to create the headache misery. CGRP is a substance present in many organs throughout the body, including the brain. It has multiple effects, depending on its target. When it is released around nerves of the head that are most associated with migraine, CGRP causes blood vessels to expand and also brings about inflammation. Both the blood vessels getting larger and the inflamed tissues hurt and probably cause the pain of migraine. The new drugs that target CGRP either block the peptide itself or the receptor structures through which it acts. CGRP medications can be divided into two distinct groups, the larger sized group, called monoclonal antibodies (Mabs), that cannot cross the barrier into the brain, and the small-sized compounds that are able to cross through the blood into the brain and other organs. The large CGRP-blocking medications are designed to prevent migraines and are given as often as every 2 weeks to monthly or less frequently. So far, they have shown no major side effects when given to patients, although potential problems of blocking CGRP on a long term basis, if any, are not yet known. Why the excitement? These Mab medications have decreased the frequency of migraine in many patients by at least 50%, and in some, about 1 in 6 patients, the migraines seemed to go completely away, at least for 3 months or longer. The small molecules, sometimes called gepants, have been studied mostly as acute, immediate, or asneeded treatments for migraine. They cross into the blood around the brain and other organs such as the liver. An earlier small molecule medication called telcagepant was found to cause liver problems in some patients, and to this day, the small molecules have not been FDA approved. The current gepants in development have not been found to cause liver problems, and they may be evaluated for both as-need treatment and prevention. The gepants are used to treat attacks as needed. They work about also on some triptans, the most commonly prescribed class of migraine-specific acute medications, but without some of the typical side effects.