Anti-CGRP Drugs Used to Treat Migraines

by Max Dakara

Migraines affect roughly 1 billion people worldwide with women being shown to suffer more migraines compared to men while before puberty, boys suffer migraines more frequently. But despite these high numbers, its etiology remains poorly understood and hence it becomes a challenge for researchers to develop a drug that can prove beneficial without adverse side effects. For individuals who gain a proper diagnosis and medication for their condition, it can become a financial burden due to the regular procurement of these drugs or the lost productivity during work due to the inability to carry out tasks during a migraine attack. On the other hand, many instances go undiagnosed and as a result, these people don’t take medication that could improve their quality of life.

So what exactly is a migraine? It is a neurological disease where an individual with the condition has a headache that’s concentrated on one side of their head. There are two major categories to differentiate migraines, migraines with aura and migraines without aura, the latter being more common in patients. A migraine with aura will include symptoms such as issues with motor skills or a brief loss of vision, 30 minutes prior to the migraine.The condition is considered chronic once an individual has experienced at least 15 migraines within a month over a span of 3 months.

Treatment in order to relieve migraines come under two categories, abortive, drugs that relieve the pain of a migraine once it starts and preventive, drugs that prevent frequent onset of migraines. A variety of medication is utilised, ranging from angiotensin-converting enzyme inhibitors which are used to treat hypertension to antidepressants. Potential medication is studied extensively and its efficacy is evaluated, usually on medication that’s used for treatment of other conditions such as depression or epilepsy. In other cases however, a possible treatment comes about which proves beneficial in treating migraines, one such case being Calcitonin Gene Related Peptide (CGRP) therapy, a preventive method of migraine treatment.

This particular treatment involves utilising drugs that targets CGRP, a 37-amino acid neuropeptide which helps in carrying out the process of vasodilation in the body. It’s been studied that this specific substance is in higher amounts in patients that suffer from chronic migraines suggesting it may be the reason for the pain brought about in a migraine.

CryoEM structure of the CGRP receptor with bound CGRP peptide in a detergent micelle

To target this specific neuropeptide, two types of anti-CGRP drugs can be utilised which are monoclonal antibodies and gepants. Monoclonal antibodies are proteins that have been manufactured to fixate on one particular substance, in this case it targets either the CGRP molecules or the receptors the CGRP binds to. This type of drug is molecularly large and hence takes time for it to carry out its function in the brain as well as only acting on the lining of the brain. Gepants on the other hand are much smaller in terms of molecular size and its entry into the brain is much quicker as a result. However, unlike monoclonal antibodies, it’s been suggested that it may lead to liver damage due to metabolism of gepants occurring in the liver.

Studies relating to CGRP migraine treatment has shown that it can greatly reduce the recurrence of migraine attacks suggested by a 2018 study where 30% of the patients saw at least a 50% decrease in the number of monthly migraine attacks. Another advantage of this particular treatment is the short-term side effects that come about, this being only irritation on the injection site as well as cases of constipation and flu like symptoms which is comparatively minor to other preventive migraine treatments. However, due to its relatively recent discovery, long term side effects still remain unknown but suggests that it may lead to hypertension due to constriction of blood vessels, with only one study suggesting otherwise. Additionally, the cost of such treatment can become a financial burden with it costing roughly US$6,900. As of now, this method of treatment is only available in the form of injectable but drugs of this kind are being developed for entry via ingestion of a pill and it is suspected to be available in the near future.

Presently, four monoclonal antibodies have been approved (erenumab, eptinezumab, fremanezumab, galcanezumab) and three gepants (ubrogepant, rimegepant sulfate, atogepant) have seen approval for the treatment by the US FDA. In time, our understanding of what exactly causes a migraine will improve and advancements in technology may aid in the discovery of its root cause or in the development of a drug that can alleviate the quality of life of the many people suffering from migraines. Along with that, as more insurance plans come about to cover the expenses that are incurred from such treatment, it can lead to it being more accessible to many and relieve the physical pain and the financial burden that comes about from the condition.

Sources:

https://migraine.com/migraine-statistics

https://www.nhs.uk/conditions/migraine/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187032/

https://americanmigrainefoundation.org/resource-library/anti-cgrp-treatment-options/

https://www.healthline.com/health/migraine/cgrp-migraine#how-its-taken

https://www.aafp.org/afp/2019/0101/p17.html#afp20190101p017-b28

https://www.drugs.com/drug-class/cgrp-inhibitors.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612904/

https://www.sciencedirect.com/science/article/abs/pii/S0140673618325340