Migraine is the sixth most prevalent disease and the second cause of disability worldwide, therefore it has a remarkable social burden. Apart from monogenic forms of migraine, several single nucleotide polymorphisms (SNPs) and epigenetic modifications have been implicated in several aspects of migraine going from susceptibility, to cortical spreading depression and aura, and to responsiveness to treatment and evolution including chronification and transformation into medication overuse headache. Classically, the genetic variants investigated for their influence on migraine development and manifestation are concerned with genes related to vascular modifications and cardiovascular diseases, such as those encoding angiotensin converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, the calcitonin gene-related peptide (CGRP) has proven a pivotal role in migraine development and sensitization, cephalic and extracephalic, addressing its progression. Moreover, most anti-migraine drugs, directly or indirectly, affect CGRP signaling. The novel four monoclonal antibodies targeting CGRP pathway, eptinezumab, fremanezumab, galcanezumab for CGRP and erenumab for CGRP canonical receptor, are the most promising tools in the arsenal for migraine treatment and prophylaxis since they are effective, well-tolerated and promising also in patients refractory to the other treatments. However, some 40% people still does not respond to mAbs. Therefore, the purpose of the present study is to identify all the genetic variants affecting the CGRP pathway to understand their possible effect on migraine susceptibility, clinical features and responsiveness to treatment. This is fundamental to future personalization of anti-migraine therapy.
Genetic variants of CGRP signaling pathway in migraine: impact on novel therapeutics
Scuteri D.;Corasaniti M. T.;
2021-01-01
Abstract
Migraine is the sixth most prevalent disease and the second cause of disability worldwide, therefore it has a remarkable social burden. Apart from monogenic forms of migraine, several single nucleotide polymorphisms (SNPs) and epigenetic modifications have been implicated in several aspects of migraine going from susceptibility, to cortical spreading depression and aura, and to responsiveness to treatment and evolution including chronification and transformation into medication overuse headache. Classically, the genetic variants investigated for their influence on migraine development and manifestation are concerned with genes related to vascular modifications and cardiovascular diseases, such as those encoding angiotensin converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, the calcitonin gene-related peptide (CGRP) has proven a pivotal role in migraine development and sensitization, cephalic and extracephalic, addressing its progression. Moreover, most anti-migraine drugs, directly or indirectly, affect CGRP signaling. The novel four monoclonal antibodies targeting CGRP pathway, eptinezumab, fremanezumab, galcanezumab for CGRP and erenumab for CGRP canonical receptor, are the most promising tools in the arsenal for migraine treatment and prophylaxis since they are effective, well-tolerated and promising also in patients refractory to the other treatments. However, some 40% people still does not respond to mAbs. Therefore, the purpose of the present study is to identify all the genetic variants affecting the CGRP pathway to understand their possible effect on migraine susceptibility, clinical features and responsiveness to treatment. This is fundamental to future personalization of anti-migraine therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
