Did you know that, according to the World Health Organisation (WHO), on average one in two people suffers from headache disorders [1]? These include migraine, tension-type headache, cluster headache and medication-overuse headache. In this article, which we publish in response to the curiosity of our readers about the topic, we will focus specifically on migraine, namely on the latest discoveries and some of the available treatments. Putting together a complete list of the latter goes beyond the purpose of this article.

Migraine is defined as a primary headache disorder, referring to the fact that it is not caused by a traumatic event or by a known disease. It mostly affects adults between 35 and 45 years of age and it occurs two to three times more often in women than in men [1]. This seems to be related to the hormonal fluctuations that women start experiencing after puberty [2]. It is a chronic disease, therefore characterised by recurring attacks of variable intensity. The pain is often felt in a single side of the head and it can last from a few hours to several days. Nausea is also very often associated with the painful attack and other symptoms, like irritability and reduced concentration, may occur during the so-called “premonitory phase”, shortly preceding the painful episode. The attack is often followed by the “postdrome” phase, characterised by a general feeling of unease and tiredness. Less frequently, the episodes may be associated with some forms of neurological deficits, collectively defined as “migraine aura”. All these symptoms are thought to derive from a dysregulation of some sensory processing in the brain and migraine is, in fact, considered by some neuroscientists “as a brain state of altered excitability” [1, 3].

The exact causes triggering the attacks are not yet fully understood [4], but research has made relevant progress in this direction in recent years. In fact, in 2021 the “Brain prize” – one of the world’s most prestigious in the field of neuroscience – was awarded to four scientists “for their groundbreaking work on the causes and treatment of migraine” [5]. Their collective efforts led to the discovery of the calcitonin gene-related peptide (CGRP) as a key factor in triggering migraine attacks. Several other endogenous molecules are being studied for their role in the onset of migraine and different kinds of drugs might be prescribed by specialists in each specific case, being migraine per se a very complex and diversified condition. Here, we will keep our focus specifically on the CGRP, since it is considered by the experts as one of the most prominent targets for migraine treatment development [6]. This peptide is produced in the brain and it has a strong vasodilator effect, along with playing a key role in modulating some neuronal functions. Its blood levels are found to be higher during a migraine attack and it is also able to trigger one, if administered to someone who chronically suffers from this disease [7].

Following these observations, two classes of drug treatments have been developed in the past years: the so-called gepants, which antagonise the effect of the CGRP, and monoclonal antibodies (monoclonal antibody) directed against the CGRP itself or one of its cellular receptors. While gepants are effective for the treatment of the acute phase, monoclonal antibodies are recommended to prevent the attacks [8, 9, 10, 11]. Among the latter, erenumab was the first to be authorised by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in 2018 [11, 12].