A new clue to the migraine puzzle

Four genes associated with the most common form of migraine have been revealed thanks to international scientific collaboration. Jean Schoenen and his team from the Headache Research Unit (University of Liège) helped to discover these first-ever genetic factors specifically linked to migraine without aura.

Migraine lumièreAlthough ‘migraine’ is a term often used to refer to a headache, it isn’t a simple cephalgia. Headache is indeed one of the symptoms of migraine if it lasts 4 to 72 hours without treatment and recurs at least five times. However, to diagnose migraine other criteria need to be present.

During an attack, at least two of the following characteristics are found: unilaterality, pulsatility, moderate to severe intensity or exacerbation of the pain by routine physical activity. In addition, the migraine attack is also accompanied by at least one of nausea and/or vomiting, photophobia and phonophobia – a heightened sensitivity to light and. As for migraines ‘with aura’, that affect one out of every five migraine sufferers, the headache is preceded by neurological disturbances, most often visual.

Conquering the genetics of migraine

The criteria used to define whether or not a patient is suffering from migraine are thus clearly established. Unfortunately, this is not the case with regard to treatment and the genetic basis of this disease which affects 16 to 18 % of the population. Jean Schoenen, director of the Headache Research Unit in the Department of Neurology & GIGA-Neurosciences at ULg, and his team are gradually retracing the genetic traces of migraines thanks to collaboration with a European consortium. Indeed, in order to to optimise migraine treatment, it is essential to discover which genetic pecularities predispose to the disease and what types of dysfunctions these genes cause in the brain.

The first genetic mutations associated with migraine were discovered in a rare subtype called « familial hemiplegic migraine”, where the attacks are accompanied by paralysis of half the body. This is a ‘monogenic’ form, so-called because a mutation in a single gene is responsible for the disorder.

In spite of more than10 years of intensive research, such a genetic abnormality affecting a single gene was never found in the common forms of migraine. It has since transpired that in these common forms, it is a combination of genetic particularities that determine a predisposition to migraine, which is why they are called ‘polygenic’. Pinpointing the combinations of genetic variants that might lead to the appearance of one or the other type of migraine is a lengthy job, which requires going through the entire human genome with a fine tooth-comb; however, this process has sped up thanks to the constantly increasing performance of genetic analyses.

In 2009, Jean Schoenen and his team, in collaboration with Italian researchers, published a study in the journal Neurology (1) showing that the mitochondrial genome can be involved in the appearance, and especially the treatment, of migraines. Based on the observation that vitamin B2 has a preventive effect on migraine attacks in some patients, the scientists sought to understand why this group of patients responded to the treatment and not the other one. They found the answer in mitochondrial DNA.

(1) C. Di Lorenzo, MD, F. Pierelli, MD, G. Coppola, MD, G. S. Grieco, PhD, C. Rengo, PhD, M. Ciccolella, BSc, D. Magis, MD, M. Bolla, MD, C. Casali, MD, F. M. Santorelli, PhD and J. Schoenen, MD., Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs. Neurology, 2009;72:1588-1594

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