Biological and small molecule strategies in migraine therapy with relation to the calcitonin gene‐related peptide family of peptides

Edvinsson, Lars; Edvinsson, Jacob C A; Haanes, Kristian Agmund

doi:10.1111/bph.15669

Cited by 16 publications

(24 citation statements)

References 83 publications

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“…Cuando la bióloga norteamericana Susan G. Amara 1 describió en 1982 el CGRP, poco podía imaginar que su descubrimiento tendría aplicaciones en la terapia de la migraña. La tabla 1 muestra los péptidos que componen la superfamilia de péptidos calcitonina/CGRP [2][3][4][5] .…”

Section: Introducción: El Péptido Relacionado Con El Gen De La Calcit...unclassified

“…Estos receptores están asociados a receptor activity-modifying proteins (RAMP). La combinación de los dos receptores con las RAMP determina la especificidad de cada péptido por su receptor (Tabla 2) [2][3][4][5] .…”

Section: Introducción: El Péptido Relacionado Con El Gen De La Calcit...unclassified

“…Ello se debe a que ambos receptores son muy similares en su secuencia de aminoácidos. Por tanto, si se desea anular totalmente el CGRP, se debe actuar sobre los receptores CLR/RAMP1 y los AMY1 [2][3][4][5] . Cabe decir que ninguno de estos péptidos cruza una barrera hematocefálica (BHE) íntegra, pues su tamaño medio es de 150 kD.…”

Section: Introducción: El Péptido Relacionado Con El Gen De La Calcit...unclassified

“…El CGRP es un neuropéptido de 37 aminoácidos que existe en dos subformas: α y β [2][3][4][5] . Las dos subformas están en el sistema nervioso y comparten los mismos receptores, difiriendo en potencia.…”

Section: Introducción: El Péptido Relacionado Con El Gen De La Calcit...unclassified

“…También está en los ganglios dorsales paraespinales y en las astas posteriores medulares. En el encéfalo se ha detectado en el tronco (locus coeruleus, núcleo del rafe, núcleo grácil y núcleo subtalámico) y en el cerebelo, tálamo, hipotálamo y ganglios basales [2][3][4][5] . Los estudios de CGRP en células gliales ofrecen datos controvertidos.…”

Section: Introducción: El Péptido Relacionado Con El Gen De La Calcit...unclassified

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Tratamiento preventivo de la migraña con fremanezumab subcutáneo

Belvís¹,

Morollón²

2022

KRANION

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El fremanezumab es un anticuerpo monoclonal (MAb) subcutáneo contra el péptido relacionado con el gen de la calcitonina (CGRP) (CGRP-MAb) recientemente aprobado para la prevención de la migraña episódica y crónica. Se revisa el mecanismo de acción de los CGRP-MAb y sus resultados en la prevención de la migraña, con especial atención al fremanezumab. Asimismo, se revisan los resultados de las dos pautas que presenta este fármaco (mensual y trimestral), pues ha suscitado interés su pauta trimestral, única entre los tres CGRP-MAb subcutáneos comercializados. Un reciente metaanálisis no ha observado diferencias de eficacia clínicamente significativas entre las dos pautas. Otro estudio ha comunicado que un 69% de los pacientes tratados con fremanezumab prefiere la pauta trimestral. Por otra parte, se analiza el fenómeno wearing-off en este fármaco, concluyéndose que no se ha constatado en ninguna de las dos pautas. Adicionalmente, se revisa la seguridad y tolerabilidad del fremanezumab en los estudios, mostrándose excelentes. En definitiva, puede afirmarse que las dos pautas de fremanezumab son similares en cuanto a eficacia en la prevención de la migraña y presentan un excelente perfil de seguridad y tolerabilidad.

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Section: Introducción: El Péptido Relacionado Con El Gen De La Calcit...unclassified

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Tratamiento preventivo de la migraña con fremanezumab subcutáneo

Belvís¹,

Morollón²

2022

KRANION

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Pituitary cyclase‐activating polypeptide targeted treatments for the treatment of primary headache disorders

Karsan,

Edvinsson,

Vecsei

et al. 2024

Ann Clin Transl Neurol

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ObjectiveMigraine is a complex and disabling neurological disorder. Recent years have witnessed the development and emergence of novel treatments for the condition, namely those targeting calcitonin gene‐related peptide (CGRP). However, there remains a substantial need for further treatments for those unresponsive to current therapies. Targeting pituitary adenylate cyclase‐activating polypeptide (PACAP) as a possible therapeutic strategy in the primary headache disorders has gained interest over recent years.MethodsThis review will summarize what we know about PACAP to date: its expression, receptors, roles in migraine and cluster headache biology, insights gained from preclinical and clinical models of migraine, and therapeutic scope.ResultsPACAP shares homology with vasoactive intestinal polypeptide (VIP) and is one of several vasoactive neuropeptides along with CGRP and VIP, which has been implicated in migraine neurobiology. PACAP is widely expressed in areas of interest in migraine pathophysiology, such as the thalamus, trigeminal nucleus caudalis, and sphenopalatine ganglion. Preclinical evidence suggests a role for PACAP in trigeminovascular sensitization, while clinical evidence shows ictal release of PACAP in migraine and intravenous infusion of PACAP triggering attacks in susceptible individuals. PACAP leads to dural vasodilatation and secondary central phenomena via its binding to different G‐protein‐coupled receptors, and intracellular downstream effects through cyclic adenosine monophosphate (cAMP) and phosphokinase C (PKC). Targeting PACAP as a therapeutic strategy in headache has been explored using monoclonal antibodies developed against PACAP and against the PAC1 receptor, with initial positive results.InterpretationFuture clinical trials hold considerable promise for a new therapeutic approach using PACAP‐targeted therapies in both migraine and cluster headache.

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Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real‐world clinical evidence in a severely impaired patient population

et al. 2023

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Background Galcanezumab is a monoclonal antibody acting against the calcitonin gene‐related peptide approved for the preventive treatment of migraine. The aim of this article is to explore its effectiveness and safety of galcanezumab in chronic migraine (CM) with medication overuse‐headache (MOH). Methods Seventy‐eight patients were consecutively enrolled at the Modena headache center and followed up for 15 months. Visits were scheduled every 3 months, and the following variables were collected: the number of migraine days per month (MDM); the painkillers taken per month (PM); the number of days per month in which the patient took, at least, one painkiller; the six‐item headache impact test; and the migraine disability assessment questionnaire (MIDAS) score. Demographic features of the analyzed sample were collected at the baseline and adverse events (AEs) were collected at every visit. Results After 12 months, galcanezumab significantly reduced the MDM, the PM, the number of days on medication, the HIT‐6 as well as the MIDAS scores (all p < .0001). The greatest amelioration was obtained in the first trimester of treatment. A higher MDM, a higher NRS score at the baseline, and a higher number of failed preventive treatments negatively predict the CM relief at the year of treatment. No serious AEs were registered and only one drop‐out was due to AE. Conclusions Galcanezumab is effective and safe for the treatment of patients affected by CM and MOH. Patients with a higher impairment at the baseline may found less benefits with galcanezumab.

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Biological and small molecule strategies in migraine therapy with relation to the calcitonin gene‐related peptide family of peptides

Cited by 16 publications

References 83 publications

Tratamiento preventivo de la migraña con fremanezumab subcutáneo

Tratamiento preventivo de la migraña con fremanezumab subcutáneo

Pituitary cyclase‐activating polypeptide targeted treatments for the treatment of primary headache disorders

Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real‐world clinical evidence in a severely impaired patient population

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