1. 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: November 30, study supported by Amgen and Novartis, which codeveloped Erenumab
Olivia
Moderator: Dr. Yugrakh
EBN February 2018

2. 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

3. 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