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Tinkering With Genes to Prevent Migraines

Tinkering With Genes to Prevent Migraines

Two new drugs in promising clinical trials use genetic engineering to prevent migraine headaches, the third most common and seventh most disabling medical disorder in the world.

Both use genetically engineered “monoclonal antibodies” attacking a new target in migraine prevention, a small protein known as the calcitonin gene-related peptide, or CGRP.

CGRP is involved in the transmission of and heightened sensitivity to pain experienced in migraine. It is critically important at the start of a migraine. CGRP also increases the heartbeat and alters sensory transmission during migraines.

CGRP is produced by neurons around the spinal cord in greater amounts than usual before and during migraines, and mediated through specific receptors. So one way of preventing migraine from occurring is to block CGRP receptors. But never before have drugs been developed to specifically target CGRP.

In the first study, Peter J. Goadsby, M.D., of the University of California, San Francisco, and colleagues investigated an anti-CGRP antibody called ALD403. Either a single intravenous dose of ALD403, or placebo, was given to 163 people who had migraines for five to 14 days per month. Migraines in the following eight weeks were recorded, and participants were followed for 24 weeks in total to observe any side-effects.

The drug was linked to an average of 5.6 fewer days of migraine per month, equating to a 66 percent decrease. However, the placebo also reduced days of migraine by 52 percent. No differences were seen in side-effects between the groups.

“A single intravenous dose of ALD403 1,000 mg demonstrated efficacy for the preventive treatment of migraine in patients with a high monthly frequency of migraine days,” the researchers noted.

They add that ALD403 was generally safe and well tolerated. “These results support the conduct of larger randomized, placebo-controlled studies and may potentially represent a new era in disease-specific and mechanism-based preventive therapy for migraine,” they conclude.

The same team carried out a second study of 217 people who had migraine four to 14 days per month. Participants received injections of another anti-CGRP antibody called LY2951742 at 150 mg, or placebo, every other week for 12 weeks.

The drug was associated with an average of 4.2 fewer migraine days per month in the following 12 weeks, that is, a 63 percent decrease. Placebo was linked to a 42 percent drop.

But this time the drug was linked to side-effects, including pain at the injection site, upper respiratory tract infections, and abdominal pain. Overall however the drug was considered to be safe and well-tolerated.

“In subjects with frequent migraine headache, treatment with LY2951742 resulted in a significant decrease in the number of migraine headache days, headache days, and migraine attacks when compared to placebo,” said the researchers. “The safety and robust efficacy results in this study are promising and justify the conduct of phase III studies,” they add.

Both were phase II studies, so larger studies are needed to confirm the results. They were presented at the American Academy of Neurology’s annual meeting in Philadelphia, PA.

The ALD403 study was supported by Alder Biopharmaceuticals of South Bothell, Washington, USA. The LY2951742 study was supported by Arteaus Therapeutics of Cambridge, Massachusetts, USA. But the rights to LY2951742 have been bought back by Eli Lilly & Co of Indianapolis, after licensing it to Arteaus for three years.

“We will do what we can to accelerate development of this drug because it involves a big patient population,” said Jan Lundberg, Eli Lilly & Co’s research chief.

Co-author on both studies, David Dodick, M.D., of Mayo Clinic Arizona in Phoenix commented, “Migraine remains poorly treated, and there are few effective and well-tolerated treatments approved that prevent attacks from occurring. There is a huge treatment need for migraine.”


Goadsby, P. J. et al. Randomized, Double-blind, Placebo-controlled Trial of ALD403: An Anti-CGRP Peptide Antibody in the Prevention of Frequent Episodic Migraine. Presented on Friday 2 May 2014 at the American Academy of Neurology’s 66th annual meeting in Philadelphia, PA.

Dodick, D. W. et al. CGRP Monoclonal Antibody LY2951742 for the Prevention of Migraine: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study. Presented on Friday 2 May 2014 at the American Academy of Neurology’s 66th annual meeting in Philadelphia, PA.

DNA pill photo by shutterstock.

Tinkering With Genes to Prevent Migraines

Jane Collingwood

Jane Collingwood is a long-time writer for Psych Central, with a background in journalism and a focus on mental health.

APA Reference
Collingwood, J. (2018). Tinkering With Genes to Prevent Migraines. Psych Central. Retrieved on September 26, 2020, from
Scientifically Reviewed
Last updated: 8 Aug 2018 (Originally: 20 Aug 2014)
Last reviewed: By a member of our scientific advisory board on 8 Aug 2018
Published on Psych All rights reserved.