More threads by David Baxter PhD

David Baxter PhD

Late Founder
CGRP: A new era for migraine treatment
by Carolyn A. Bernstein, MD, FAHS, Harvard Health Blog
March 5, 2018

Migraine is a common medical condition, affecting as many as 37 million people in the US. It is considered a systemic illness, not just a headache. Recent research has demonstrated that changes may begin to occur in the brain as long as 24 hours before migraine symptoms begin. Many patients have a severe throbbing headache, often on only one side of the head. Some people are nauseated with vomiting. Many are light sensitive (photophobic) and sound sensitive (phonophobic), and these symptoms can persist after the pain goes away.

There are a variety of migraine subtypes with symptoms that include weakness, numbness, visual changes or loss, vertigo, and difficulty speaking (some patients may appear as if they are having a stroke). The disability resulting from this chronic condition is tremendous, causing missed days of work and loss of ability to join family activities.

It is sometimes possible for people to use an “abortive” medication, which, when taken early, can arrest the migraine process. For many patients, a preventive medication can decrease both the frequency and the severity of the migraines. But to date, many of the medications available for migraines have been developed primarily for other causes: seizures, depression, high blood pressure, and muscle spasms, for example. Researchers have been working for decades to develop a “targeted” preventive therapy specifically for migraine, and now we are finally close to having an exciting new treatment.

What does “targeted” therapy mean?
Calcitonin gene-related peptide (CGRP) is a molecule that is synthesized in neurons (nerve cells in the brain and spinal cord). It has been implicated in different pain processes, including migraine, and functions as a vasodilator — that is, it relaxes blood vessels. Once scientists identified this target molecule, they began trying to develop ways to stop it from being activated at the start of migraines, as a kind of abortive treatment. An agonist makes a molecule work more efficiently, and an antagonist blocks or reduces the molecule’s effect. The CGRP antagonist did work to decrease migraine pain based on certain measures, but there were some serious side effects including liver toxicity.

Back to the drawing board.

Monoclonal antibodies: Cutting-edge translational science
You have likely seen ads for monoclonal antibody (mAb) cancer and autoimmune therapies. There are lots of different types of mAbs, and while some harness a person’s own immune system to block replication of cancer cells, others stop a reaction in the body by binding to a target molecule or receptor and inhibiting it, thus preventing the reaction from continuing. The CGRP mAbs have this effect, and because they have a long duration of action (called a half-life), they can be administered much less frequently than typical migraine medications that are taken daily (with the exception of botulinum toxin, which is injected every 90 days). These new migraine medications are injected under the skin monthly, and have thus far demonstrated a statistically significant decrease in days of migraine. Four different drug companies are developing these new molecules, with two versions already sent to the FDA for approval.

What’s next?
If you think you may be a candidate for this new type of migraine medication, talk with your doctor, and perhaps ask for a consult with a neurologist or headache specialist who can help you understand more about the medication. Monoclonal antibody therapy is expensive, and there will likely be regulations about for whom s the treatments are appropriate. Much more research needs to be done about who is the best candidate for this therapy. But for many migraine patients who have not responded to the standard treatments, or who have had intolerable side effects such as cognitive dysfunction, low blood pressure, weight loss or gain, or other issues, CGRP monoclonal antibodies are safe and well tolerated, and are an exciting new development for migraine therapies.
 
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