CGRP: What You Need to Know

By Dr. James Banks, National Headache Foundation Board Member

What is CGRP?

First, some background: CGRP is the abbreviation for Calcitonin Gene-Related Peptide, a protein in the brain and nervous system involved in the transmission of pain and the resultant reaction of tissues and blood vessels. The new medications you are hearing about are actually monoclonal antibodies to either the CGRP itself or the receptors where CGRP lands. 

There are various forms of CGRP in different parts of the body. They all have very different actions. These new drugs are very specific for the nerves and blood vessels involved in migraine.

What are monoclonal antibodies?

Monoclonal means all the antibodies are made from the same genetic material. They are grown in living humanized cell cultures. The antibodies are also made repeatedly, over and over, so that they are all identical. This process is very difficult and expensive. 

Antibodies are proteins that counter or interfere with very specific parts of another protein or the locations where a protein is supposed to bind to the receptor. These are most known in regards to preventing or fighting off infections. For example, the vaccines used to help prevent measles, mumps, rubella, and influenza (among others). In these antibodies, there is a small portion of the infectious material of the virus or bacteria—the antigen—which is recognized by the body. The body produces antibodies that, in simple terms, float around the body waiting for a signal to activate and attach to the antigen. This blocks the virus from attaching to cells and furthering the infection.  It is the body’s defense system.

Monoclonal antibodies have been developed to more precisely target specific processes in the body.  Monoclonal antibodies are already being used in treating some cancers and autoimmune diseases. 

How does the CGRP Medication Work?

In the case of the new monoclonal antibodies to CGRP, or CGRP antagonists, antibodies have been created that when administered to an individual with migraine will block the receptor sites on blood vessels or attach to CGRP itself so that it cannot fit into the receptor sites and thus interferes with the series of events that leads to migraine.

One way to visualize this is to think of a parking lot.

You have a special car, say a large blue CGRP van, and there are only certain spots in which your car can fit to park (receptors). One brand of the new anti-CGRP drugs (the white van) fills up those parking spaces (by binding to the receptors), thus preventing your van from being able to park (Figure 1).

Figure 1

The other CGRP antagonist drugs work by circulating around the parking lot on the lookout for CGRP vans. When they detect a van, they attach to the van so that it no longer fits into the parking spot (Figure 2).

Figure 2

If the CGRP van cannot park, it gives up and leaves. The process of migraine does not start or it is only a mild attack.

Because these antibodies remain active in the body for weeks or months, the migraine process is inhibited for that period of time. This is unlike the triptan medicines which stay in the body for only hours. Triptans, however, work much differently.

There are a lot of things about these CGRP antagonist drugs that make it appear to be ideal for the prevention of migraine. Up until now, all the other drugs used for migraine prevention were originally developed and marketed for other conditions. Some of these conditions are quite unlike migraine. These new anti-CGRP antibodies are the first to be developed against the specific processes of migraine.

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