There is extensive research being conducted globally on migraine medications, with major advances made in treatment in recent years. While these new drugs can help a significant proportion of patients, they unfortunately do not provide satisfactory relief for everyone. According to the leader of the HUN-REN–University of Szeged Neuroscience Research Group, their research could bring us closer to discovering new therapeutic options.
Migraine is often associated with unbearable suffering, but this is not the only reason it is considered one of the most significant neurological disorders. It affects between 10 and 16% of the world's population—more than 1 million people in Hungary alone—and is more common in women than men. Globally, nearly a billion people live with these highly uncomfortable headaches as part of their daily lives. "Therefore, any result that reduces patient suffering has a significant economic impact. After all, someone may be physically present at work, but if they have a migraine, they are unable to perform their tasks effectively," emphasised Professor Dr László Vécsei, leader of the HUN-REN–SZTE Neuroscience Research Group.
Clinically, migraines can be divided into two main categories: migraine with aura and migraine without aura. Migraines with aura are characterised by certain warning signs and other symptoms that accompany the headache, such as visual disturbances. Additionally, several types of migraines can be identified based on their clinical presentation. These include basilar migraine (which can involve visual and speech problems), the rare hemiplegic migraine (which may cause weakness or paralysis on one side of the body), chronic migraine (where episodes typically occur for 15 days per month over a 3-month period), menstrual migraine, retinal migraine, and various other clinical forms.
Proper stress management, along with good quality and sufficient sleep, can reduce the likelihood of migraines. However, it is undeniable that a certain degree of genetic predisposition also plays a role in their development. In other words, the combined effect of several genes can increase the likelihood of experiencing headaches. Environmental factors can also contribute—for example, some people develop migraines in response to changes in the weather. A stressful lifestyle and lack of sleep can also trigger these attacks. Dr László Vécsei added that some studies suggest people with migraines have a slightly higher statistical risk of stroke than those without the condition, and there is also a link between migraines and epilepsy.
Dr László Vécsei's research group in Szeged is currently investigating the relationship between migraine and the kynurenine system, an area that has received relatively little attention in previous studies. In their latest publication, they reviewed the roles of the nervous and immune systems from the perspective of alterations in kynurenine metabolism.
Tryptophan is an essential amino acid that cannot be produced by the body and must be obtained from the diet. Kynurenines are the primary products of tryptophan metabolism, as this amino acid is predominantly converted into kynurenine. Through the kynurenine pathway, tryptophan is transformed into a wide range of biologically active molecules that play a crucial role in the functioning of the immune and nervous systems.
One such metabolite is kynurenic acid, which inhibits neuronal activity, while another molecule, quinolinic acid, activates it. These molecules also play an important role in regulating the immune system. In previous clinical studies, the Szeged research group found significant changes in kynurenine metabolism in both migraine and cluster headache patients.
"However, in addition to kynurenine, a peptide known as PACAP also plays an important role in the pathogenesis of migraine," says Dr László Vécsei, whose research has shown that blood levels of PACAP are elevated in migraine patients. This is one of the reasons why personalised medicine is necessary, he explains, as almost 40 per cent of patients do not respond adequately to migraine drugs based on the recently developed CGRP inhibitors (CGRP is a protein that plays a key role in triggering and maintaining migraines and other types of chronic headache). It is also worth noting that one of their kynurenic acid analogues has been shown to reduce PACAP levels in a published experimental migraine model.
In summary, monitoring the individual patient's metabolism and the associated molecular biomarkers can offer important insights for personalised medicine. Researchers are still in the early stages of drug development, so it is unlikely that patients who do not respond well to current medications will find relief next year.