What Are Anti-CGRP Treatments and How Do They Work?
Learn about the targeted mechanism of anti-CGRP medications and how they work within the nervous system to address the underlying biology of migraine.
Calcitonin Gene-Related Peptide (CGRP) is a protein that naturally exists in the nervous system and has various functions throughout the body. For years, scientists have understood its general roles, but more recent investigations have solidified its connection to specific medical conditions, most notably migraine headaches. This understanding paved the way for a new category of medications known as anti-CGRP therapies. These treatments are specifically designed to interact with the CGRP pathway, offering a targeted approach for managing conditions linked to this molecule.
The Role of CGRP in Migraines
CGRP is a neuropeptide, a protein-like molecule used by neurons to communicate, and it is particularly abundant in the trigeminal nervous system. This network of nerves is responsible for sensations in the face and head. Normally, CGRP contributes to processes like the widening of blood vessels, known as vasodilation, and plays a part in transmitting pain signals. This function is part of the body’s standard operational network for maintaining blood flow and responding to stimuli.
During a migraine attack, the role of CGRP becomes more pronounced. Studies have consistently shown that CGRP levels in the cranial circulation increase significantly during these episodes. This flood of CGRP is believed to contribute directly to the debilitating symptoms of a migraine. The peptide causes the blood vessels surrounding the brain to dilate and promotes a condition called neurogenic inflammation, where nerve activation leads to the release of inflammatory substances.
This release of inflammatory molecules further sensitizes the nerve endings. The combination of dilated blood vessels and heightened nerve sensitivity amplifies pain signaling within the trigeminal system. Essentially, CGRP acts as a messenger that initiates and sustains the cascade of events leading to the intense, throbbing pain and other sensory disturbances characteristic of a migraine attack.
How Anti-CGRP Therapies Function
Given the clear involvement of CGRP in migraine attacks, therapies were developed to specifically interrupt its activity. These treatments work by targeting the CGRP pathway in one of two primary ways. The first strategy involves medications that bind directly to the CGRP molecule itself. This action effectively neutralizes the peptide, preventing it from ever reaching and activating its designated receptors on other cells.
A second, slightly different approach involves targeting the CGRP receptor instead of the molecule. The CGRP receptor is a structure on the surface of cells that CGRP must dock with to deliver its message. By designing a medication that physically blocks this receptor, the therapy prevents CGRP from binding, even when it is present in high amounts. This blockade effectively stops the signal that would otherwise lead to vasodilation and pain transmission.
Available Anti-CGRP Medications
The class of anti-CGRP treatments includes two main categories of drugs: monoclonal antibodies and a class of small molecules called gepants. Monoclonal antibodies are proteins engineered in a laboratory that are designed to recognize and bind to a single, specific target. In the case of migraine prevention, some of these antibodies, like fremanezumab and galcanezumab, are designed to attach to the CGRP ligand—the molecule itself. Another, erenumab, is designed to attach to the CGRP receptor.
These antibody-based therapies are primarily used for migraine prevention. Because they are large protein molecules, they are not taken orally but are administered through injections. Their structure allows them to remain in the body for an extended period, providing a sustained preventive effect against migraine attacks.
Gepants represent a different type of medication; they are small molecules that also block the CGRP receptor. Their smaller size allows them to be formulated as oral tablets. This class of drugs offers versatility in treatment, with some, such as ubrogepant and rimegepant, approved for stopping a migraine attack that is already underway. Other gepants, including atogepant and rimegepant, are used for the prevention of migraines.
Application of Anti-CGRP Treatments
Anti-CGRP treatments are prescribed primarily for the management of migraine headaches. They are often considered for individuals who experience frequent or highly debilitating migraines. These therapies may also be an option for patients who have not found relief with other types of migraine medications or who have had difficulty tolerating the side effects of older treatments. The choice between a preventative antibody and an acute or preventative gepant is a decision made between a patient and their healthcare provider, based on the frequency and severity of migraines, lifestyle, and overall health.