Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech Drugs

Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is...

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Main Authors: Damiana Scuteri, Paolo Martelletti
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Toxins
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Online Access:https://www.mdpi.com/2072-6651/17/7/355
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author Damiana Scuteri
Paolo Martelletti
author_facet Damiana Scuteri
Paolo Martelletti
author_sort Damiana Scuteri
collection DOAJ
description Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies.
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spelling doaj-art-fa09a164b4ef40f3a2206db3385ff1ca2025-08-20T03:08:00ZengMDPI AGToxins2072-66512025-07-0117735510.3390/toxins17070355Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech DrugsDamiana Scuteri0Paolo Martelletti1Department of Health Sciences, University “Magna Graecia” of Catanzaro, 88100 Catanzaro, ItalySchool of Health, Unitelma Sapienza University of Rome, 00161 Rome, ItalyMigraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies.https://www.mdpi.com/2072-6651/17/7/355migraineonabotulinumtoxin Aepigeneticsserum miRNAsDNA methylationCGRP
spellingShingle Damiana Scuteri
Paolo Martelletti
Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech Drugs
Toxins
migraine
onabotulinumtoxin A
epigenetics
serum miRNAs
DNA methylation
CGRP
title Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech Drugs
title_full Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech Drugs
title_fullStr Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech Drugs
title_full_unstemmed Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech Drugs
title_short Translational Impact of Genetics and Epigenetics of CGRP System on Chronic Migraine Treatment with Onabotulinumtoxin A and Other Biotech Drugs
title_sort translational impact of genetics and epigenetics of cgrp system on chronic migraine treatment with onabotulinumtoxin a and other biotech drugs
topic migraine
onabotulinumtoxin A
epigenetics
serum miRNAs
DNA methylation
CGRP
url https://www.mdpi.com/2072-6651/17/7/355
work_keys_str_mv AT damianascuteri translationalimpactofgeneticsandepigeneticsofcgrpsystemonchronicmigrainetreatmentwithonabotulinumtoxinaandotherbiotechdrugs
AT paolomartelletti translationalimpactofgeneticsandepigeneticsofcgrpsystemonchronicmigrainetreatmentwithonabotulinumtoxinaandotherbiotechdrugs