Abstract Details

Title Erenumab (AMG334) An Antagonist to Canonical CGRP-Receptor Does Not Impair Vasodilatory or Contractile Responses to Other Agents In Human Isolated Cerebral Arteries

Topic Headache

Presentation(s) S17 - Headache: Clinical Trials I (1:11 PM-1:22 PM)

Poster/Presentation
Number 002

Objective Given that CGRP can mediate vasodilation, we investigated the effect of erenumab on vasoactive agent responses to CGRP and other mediators using isolated human cerebral and meningeal arteries in the presence/absence of various vasodilatory (e.g. CGRP) and of several vasocontractile mediators.

Background Calcitonin gene-related peptide (CGRP) is a neuronal transmitter involved in migraine pathophysiology and in other biological functions. Recently, a monoclonal antibody to the canonical CGRP receptor, erenumab (AMG334), showed significant prophylactic efficacy and favorable safety in phase II and III clinical trials for migraine.

Design/Methods Ring segments of human isolated cerebral and meningeal arteries were mounted in a sensitive myograph. Functional responses were studied by first inducing pre-contraction with 30 mM potassium chloride (KCl), followed by administration of CGRP in increasing concentrations (0.1 nM–0.1 mM) in the absence/presence of different erenumab concentrations. Additionally, contractile responses to sumatriptan and dihydroergotamine, and relaxant responses to substance-P and nicardipine were examined.

Results 30 mM KCl showed stable contraction and CGRP induced a concentration-dependent relaxation. We observed that (i) erenumab had no direct contractile or relaxant effects, (ii) pre-treatment with erenumab antagonized CGRP-induced relaxation in a competitive manner, (iii) relaxant responses to substance-P and nicardipine were unaffected in the presence of erenumab and (iv) the contraction induced by sumatriptan or dihydroergotamine were unmodified by erenumab.

Conclusions Our findings demonstrate the specific inhibitory effect of erenumab of CGRP-induced relaxation, while it is not associated with vasoconstrictive effect and does not impact vasorelaxant or contractile responses of other relevant vasoactive agents in human biology.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Cen Xu, PhD (Amgen Inc.)	No disclosure on file
Josefin Snellman	No disclosure on file
Lars Edvinsson	No disclosure on file

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