Olivia Moderator: Dr. Yugrakh EBN February 2018 A Controlled Trial of Erenumab for Episodic Migraine. AMG334 /Aimovig™ Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. N Engl J Med 2017; 377:2123-2132 November 30, 2017 --study supported by Amgen and Novartis, which codeveloped Erenumab Olivia Moderator: Dr. Yugrakh EBN February 2018
Why? Same as for lasmiditan EBN Migraine 6th cause of disability worldwide Learning about migraine specific treatments helps understand migraine pathophysiology It is cool we will practice in an era with migraine specific treatments
Calcitonin gene‑related peptide (CGRP) 37 amino acid neuropeptide CGRP α gene (CALCA) encodes 2 different mRNAs which encode: 1.calcitonin, mostly in thyroid 2. αCGrP, mostly CNS CGrP gene has been discovered βCGrP gene is primarily expressed in the enteric sensory Functional CGRP receptor is a 7 transmembrane G protein coupled receptor (CLR -calcitoninlike receptor) that forms a complex w ramP1 (receptor activity modifying protein 1) RAMP1 controls surface expression of the CGRP receptor by modulating the trafficking of mature CLR proteins to the cell membrane and defining the relative potency of ligands CGRP receptors are widespread in CNS and PNS including hypothalamus and periventricular gray, unmyelinated Cfibers and thinly myelinated aδfibers, vagus n., smooth muscle layer of dura arterial blood vessels In cranial vasculature, CGrP is expressed in sensory nerve fibers, which project to the trigeminal nucleus caudalis and, to C1–3 Involved in nociceptive processing in dorsal horn SC and neuromodulation at level of cerebellum (receptors found in inhibitory interneurons) CGRP role in the trigeminovascular reflex CGRP‑containing nerve cell bodies in the trigeminal ganglion co‑localize with substance P 50% neurons in trigeminal ganglion store CGRP CGRP is released in trigeminal neuralgia, migraine, cluster attacks. CGRP antagonist olcegepant treats migraine attacks w similar efficacy to triptans CGRP promoter activity decreases 2-3x w 5Ht1B/1D agonists such as sumatriptan Main idea: CGRP is involved in the triggering of migraine, and CGRP receptor antagonists could potentially preventive