A migraine headache is an intense pulsing or throbbing pain, lasting for 4-72 hours if left untreated. Associated symptoms can include nausea, vomiting, and sensitivity to light, smell, or sound. Migraine headaches can also be associated with an “aura”, consisting of visual anomalies such as flashing lights, or loss of vision. Migraines affect approximately 10% of people, women more than men. The most common triggers for migraine appear to be stress, anxiety, bright/flashing lights, changes in hormones, and dietary factors.
Current therapy for migraine headaches includes both prevention and treatment strategies. Certain medications that have been used for other conditions such as epilepsy or depression have also been used to prevent migraines. In addition to medication, behavioural changes can help prevent the onset of migraine headaches including: stress management, relaxation techniques, and exercise. Once a migraine headache has already begun, medications such as sumatriptan, ergotamine drugs, and analgesics can be used to treat the symptoms.
Migraine headaches are still incompletely understood, however, it is believed that genetic mutations are involved, which result in neurological abnormalities. A better understanding of the underlying causes of migraine headache and the specific mechanisms involved will lead to better treatment strategies and targeted drugs that are specifically designed to treat them.
Calcitonin gene-related peptide (CGRP) is a protein that has been implicated in the pathophysiology of migraine headaches. It is involved in the transmission of the pain signal in the body. During a migraine headache, the CGRP protein binds to and activates its receptors, thereby activating a pain signal. Targeting of CGRP would therefore inhibit the activation of its receptors, ultimately inhibiting the transmission of the pain signal. In this way, the migraine attack would be prevented, rather than treated after it has already begun.
Two antibodies targeted to CGRP have recently been the subject of phase II clinical trials for those suffering from migraine headaches. The drugs have shown great promise, and the results of the studies were recently presented at the American Academy of Neurology’s 66th Annual Meeting in Philadelphia.
LY2951742, a human monoclonal antibody, was assessed for safety and efficacy in a study of 217 patients who suffer from migraine headaches. In this study, patients who suffer from migraine headache between 4 and 14 days per month were randomized to either a treatment group or placebo group. The treatment group received injections of LY2951742 (150mg) twice a week for 12 weeks, while the placebo group received an injection with no medicine. The endpoints of the study were the number of headaches in the 12 week period, and the number of headache days and migraine attacks.
The study found a 62.5% decrease in migraine headaches in the treatment group, compared to a 42.3% decrease in the placebo group. Patients treated with LY2951742 had a significant reduction in headache days, migraine attacks, and responder rate when compared to the placebo group. The drug was well tolerated; however, some of the side effects noted were pain at the site of injection, respiratory tract infections, and abdominal pain.
ALD403 is another antibody targeted against CGRP. It was assessed for safety and efficacy in the prevention of migraine headache in 174 patients over a 24 week study period. In this study, patients who suffered from 5 to 14 migraine days per month were randomly assigned to the treatment or placebo group. Patients in the treatment group received a single 1000mg intravenous dose of ALD403 at the beginning of the study. There was a 66% decrease in migraine days in the treatment group compared to a 52% decrease in the placebo group.
These targeted therapies have shown promising results so far in clinical trials, with significant reductions in the number of migraine headache days and migraine attacks compared to placebo controls. They have acceptable safety profiles, and are specifically designed to target signaling pathways involved in the onset of migraine headache. This new form of specific, preventive medicine for migraine headache holds much promise and is supportive of larger clinical trials to assess their potential benefits.
Press release available from:http://www.eurekalert.org/pub_releases/2014-04/aaon-ndo041614.phpLast Accessed: April 23, 2014.
Abstracts for the American Academy of Neurology’s 66th Annual Meeting. Available from: https://www.aan.com/conferences/2014-annual-meeting/browse-abstracts/Last Accessed: April 23, 2014.
About Migraine – Patient Information Page. Available from: http://patients.aan.com/disorders/index.cfm?event=view&disorder_id=987Last Accessed: April 23, 2014.
Image courtesy of Michal Marcol / FreeDigitalPhotos.net
Written by Deborah Tallarigo, PhD