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CGRP migraine


By Li Dali, Ph.D.

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Migraine affects a significant portion of the adult population in most countries, with a higher incidence in females. This neurological disorder is marked by recurring, severe headaches that can cause disability, as well as sensitivity to light and sound, nausea, vomiting, and, in some cases, an aura at the onset of an attack. While there is ongoing discussion, many experts believe that migraine is linked to dysfunction in the central nervous system, with involvement of different parts of the trigeminal system contributing to associated symptoms.

CGRP is a highly specific migraine trigger that can cause various migraine-like symptoms in animals, such as pain, when infused similarly to humans. Rodents administered with CGRP can exhibit mechanical hypersensitivity, a prevalent migraine symptom.

Although preclinical and clinical studies have demonstrated the significance of calcitonin gene-related peptide (CGRP) in the pathophysiology of migraines, the specific mechanisms through which it operates have yet to be fully understood.

The utilization of antibodies or small molecules to target CGRP or its receptor has proven to be highly efficacious in mitigating migraine symptoms in approximately 50% of patients.

So far, research has shown that CGRP is both necessary and sufficient to trigger migraines in a significant number of patients. Additionally, drugs that target CGRP or its receptor have proven to be effective in treating migraines. In the following section, we will discuss the safety concerns surrounding monoclonal antibodies and offer some speculation on the future direction of the field.

Despite the initial approval of molecules that target CGRP or its receptor, ongoing research aims to uncover the specific role and mechanisms of CGRP in the pathophysiology of migraines. Advancing our understanding of CGRP signaling in both normal and abnormal conditions is essential for improving current and future migraine treatments.

Another approach to consider, alongside targeting central CGRP actions, is investigating the involvement of the AMY1 receptor in migraine. Blocking AMY1 may prove to be more effective than blocking the canonical receptor for certain patients. Although AMY1 is expressed in the trigeminovascular system and CNS, its role in migraine pathophysiology remains largely unknown. Additionally, if the AMY1 receptor is implicated in migraine, it raises the question of whether the peptide amylin can also trigger migraine symptoms similar to CGRP. Ongoing preclinical and clinical studies are exploring the potential role of amylin in migraine.

Follow the link of the selected polymorphism to read a brief description of how the selected polymorphism affects Migraine and see a list of existing studies.

SNP polymorphisms related to the topic Migraine:

rs4379368The rs4379368 polymorphism may be a genetic marker for migraine patients.
rs2651899The PRDM16 rs2651899 polymorphism is a risk factor for patients with common migraine.
rs10504861rs10504861 is a SNP located on chromosome 8q21 that has been found to be associated with an increased incidence of migraine without aura in whole-genome association studies.

About The Author
Li Dali Li Dali

Li Dali, a National Foundation for Outstanding Youth Fund recipient, is a researcher at the School of Life Sciences in East China Normal University. He earned his PhD in genetics from Hunan Normal University in 2007 and conducted collaborative research at Texas A&M University during his doctoral studies. Li Dali and his team have optimized and innovated gene editing technology, leading to the establishment of a world-class system for constructing gene editing disease models.

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