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Game Changer

Receptors, Game Changer

Monoclonal antibodies specifically bind to the peptide CGRP or its receptor, thereby selectively neutralizing CGRP and its migraine-causing effects. Image: Courtesy of Dr. Andrew Charles

by Veronique de Turenne

For anyone who has white-knuckled his or her way through the explosive pain of a migraine attack, the craving for release can be extreme. Yet current avenues for relief have offered mixed effectiveness. That may soon change as the first generation of drugs that have been developed specifically for the prevention of migraine become available. The Food and Drug Administration approved one such drug, erenumab-aooe, this May.

Known as monoclonal antibodies, erenumab-aooe and several other similar drugs still in late-stage testing have been so effective in clinical trials that some experts in the field of migraine are using exuberant language like “game changer.” Like the naturally occurring antibodies in our bodies, which help to power our immune systems, lab-made monoclonal antibodies are proteins that pursue specific targets. But because the lab-made antibodies are produced by clones derived from one parent cell, they can be designed to bind to and neutralize a single, highly specific target. As scientists continue to decode a growing number of diseases at a molecular level, they increasingly are turning to monoclonal antibodies for precision therapies.

In cancer treatment, for example, monoclonal antibodies are used to carry substances like drugs or radiation directly to specific types of cancer cells. In recent Ebola research, they have shown promise in delivering a gene that will jump-start a patient’s immune response to the deadly virus. And in the migraine-prevention breakthrough, scientists have created monoclonal antibodies that target calcitonin gene-related peptide (CGRP), a neuropeptide that is known to play a role in migraine.

Researchers have found that serum concentrations of CGRP become elevated during a migraine attack, and they normalize when the attack resolves. Infusion of CGRP in patient volunteers provokes migraine attacks that are very similar to those that occur spontaneously. Small molecule drugs binding to the CGRP receptor were able to abort migraine attacks. It was this body of evidence that led researchers to suspect that by blocking CGRP receptors, or targeting the neuropeptide itself, a migraine attack could be prevented.

According to results from late-stage clinical trials of erenumab-aooe and other anti-CGRP antibodies, the researchers were right. For a subset of patients, these treatments are remarkably effective in preventing migraine, and they work quickly and have a long duration of action.

“The notion that we would be using antibodies to treat migraine is really quite a radical concept,” says Andrew Charles, MD ’86 (RES ’90, FEL ’92), Meyer and Renee Luskin Chair in Migraine and Headache Studies and director of the UCLA Goldberg Migraine Program. “This is a very different approach because, in contrast to other treatments that we’ve used in the past, which often have been developed for other reasons and we’ve borrowed them as migraine treatments, this has been developed based on our understanding of the chemistry of migraine and what is going on during a migraine attack.”

Sufferers anxious for a therapy that can head off an attack before it becomes incapacitating are understandably eager. So, too, are the physicians who will treat them. “It has all of us very excited, and we are looking forward to getting our hands on these new medications to help our patients,” Dr. Charles says.

Veronique de Turenne is a freelance writer in Los Angeles.


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Spring 2018

Spring 2018
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IN THIS ISSUE
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  • Genomic Blood Test Predicts Post-surgery Survival Rates for Advanced Heart Failure
  • Scientists Create Cells that Enable Sense of Touch
  • How Diabetes in Pregnancy Affects Baby’s Heart
  • Cancer Defense Mechanism Could Be Turned Back to Attack Tumors
  • Studying Development of Embryonic Heart Cells in Mice, Scientists Hope to Regenerate Damaged Tissue
  • Brain Trust
  • Gene Chaser
  • Gene Chaser Interview: Expanded Version
  • The L.A. Generation Xchange Project
  • Pain Like No Other
  • Game Changer
  • A Dreamer's Tale
  • Twice Blessed
  • Combat Medic
  • Awards & Honors | Spring 2018
  • In Memoriam | Spring 2018
  • RAP Stars
  • The Indelible Mark of the Rosenfeld Family
  • An Evening Remembering Leonard Nimoy
  • Inaugural C.G. Jung Symposium Explores Trauma and Healing
  • UCLA Promotes Empowered Aging with TEDxUCLA Salon
  • UCLA Department of Neurosurgery Welcomes New Chair
  • Grey Matters: Unveiling Mysteries of Brain Disease
  • Golden Portal Fundraiser Recognizes Tenacity
  • Gifts | Spring 2018
  • Leo & Me
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