a molecular biomarker enables personalization

Members of the Vall d’Hebron research team.

During an attack of migraine, several substances are released that are related to pain. One of them is the calcitonin gene-related peptide (CGRP, for its acronym in English), which is a therapeutic target commonly used for the treatment of migraine through drugs that block it. This therapy, however, is not effective in all cases. Now, the Headache and Neurological Pain group at the Vall d’Hebron Research Institute (VHIR) has measured the levels of this protein in saliva during migraine attacks and has observed that there are two types of attacks: those in which increases CGRP and those in which does not increase.

As the researchers point out in the peer-reviewed study published in Cephalalgia, describing the migraine at the molecular level and understanding the differences between individuals can help to establish a classification between types of migraine and approaches towards the personalized medicine.

It should be remembered that migraine is a very prevalent disease, which more frequently affects women, for which there are no biomarkers that can be used for the diagnosis of the disease or for the prediction of the efficacy of the treatment. With the aim of understanding its biological mechanisms and looking for biomarkers, the Vall d’Hebron project has studied the levels of the CGRP protein.

They have been analyzed in saliva samples, since obtaining it is not invasive and can be easily obtained repeatedly. Allows, therefore, to make a monitoring over time unlike, for example, a blood sample”, explains Patricia Pozo Rosich, head of the Department of Neurology at Vall d’Hebron University Hospital, head of the Headache and Neurological Pain group at VHIR and head of the Migraine Adaptive Brain Center of Vall d’Hebron. Until now, it was usual to measure it in blood, but, in addition to being more difficult to obtain, the results were inconclusive.

The study involved 22 women with sporadic migraine and 22 without headache, aged between 18 and 65 years. All of them were followed up for 30 days. On the first day, a blood sample was taken, and for the rest of the month, the participants had to take saliva samples every morning. In case of suffering a migraine attack, they also had to take a saliva sample at three times: at the beginning of the attack, 2 hours later and 8 hours later. In total, it was possible to study 49 migraine attacks.

Higher CGRP levels in women with migraine

First, CGRP levels were compared between control women and women with sporadic migraine. Specifically, CGRP measurements on headache-free days were taken into account. The results showed that, despite large differences between people, on average, the levels of protein were almost twice as high in people with migraines.

These differences were not observed in plasma, which reinforces the use of saliva to measure CGRP. The researchers of the work defend that the levels in saliva are a sample of the activation of the trigeminovascular system and from local inflammation in the head region. It therefore seems that measurement in saliva, near the region where CGRP is released during migraine, would be more effective than in blood.

The increase in CGRP during migraine attacks: towards the molecular classification of the disease

In addition to the differences between people, the study focused on analyzing the change in CGRP levels in the same person during a migraine attack. It was found that the levels of CGRP increase during the attack and decrease again once it has passed.

“This is the first study to show a gradual change in CGRP levels during the attack and gives us more information about the molecular mechanisms of migraine, that until now is only diagnosed based on clinical criteria based on symptoms. It could, therefore, be a molecular biomarker to monitor migraine”, explains Alicia Alpuente, a specialist in the Neurology Service of the Vall d’Hebron University Hospital and a researcher in the VHIR Headache and Neurological Pain group. The work is part of her doctoral thesis and she hopes to continue the research with a larger sample of patients.

But these changes in CGRP levels during the migraine attack were not clearly seen in all attacks. The researchers and researchers identified that this happened in the 79.6 per of attacks, which are considered dependent on CGRP. In contrast, 20.4 percent did not depend on CGRP. Considering seizures in a single patient, 13 of the 22 patients had only CGRP-dependent seizures, 3 had only non-CGRP-dependent seizures, and 6 of them had both types of seizures.

Also, depending on whether or not the attack was dependent on CGRP, some associated symptoms determined. In addition to pain, those dependent on CGRP had more classic migraine symptoms, such as photophobia and phonophobia. Those not dependent CGRP, on the other hand, were more associated with symptoms such as dizziness.

“This study allows begin to describe migraine at the molecular level and understand the differences between individuals, which can help establish a classification based on molecular biology and brings us closer to a future of precision medicine. If we understand the pathophysiology of migraine, in the future, we could offer an appropriate personalized treatment based on the characteristics of each patient”, Alpuente concludes.

Although it may contain statements, data or notes from health institutions or professionals, the information contained in Medical Writing is edited and prepared by journalists. We recommend the reader that any questions related to health be consulted with a health professional.

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