A pharmacogenomic evaluation of migraine therapy

Abstract

Migraine is a common idiopathic primary headache disorder with significant mental, physical and social health implications. Accompanying an intense unilateral pulsating head pain other characteristic migraine symptoms include nausea, emesis, phonophobia, photophobia and in approximately 20-30% of migraine cases, neurologic disturbances associated with the aura phase. Although selective serotonin (5-HT) receptor agonists (i.e., 5-HT(1B/1D)) are successful in alleviating migrainous symptoms in < or = 70% of known sufferers, for the remaining 30%, additional migraine abortive medications remain unsuccessful, not tested or yet to be identified. Genetic characterization of the migrainous disorder is making steady progress with an increasing number of genomic susceptibility loci now identified on chromosomes 1q, 4q, 5q, 6p, 11q, 14q, 15q, 17p, 18q, 19p and Xq. The 4q, 5q, 17p and 18q loci involve endophenotypic susceptibility regions for various migrainous symptoms. In an effort to develop individualized pharmacotherapeutics, the identification of these migraine endophenotypic loci may well be the catalyst needed to aid in this goal. In this review the authors discuss the present treatment of migraine, known genomic susceptibility regions and results from migraine (genetic) association studies. The authors also discuss pharmacogenomic considerations for more individualized migraine prophylactic treatments.

Vascular Actions of Estrogens: Functional Implications

“…Several genetic polymorphisms are associated with familial migraine including genetic variation in ER␣ (G594A polymorphism of exon 8) (Colson et al, 2004(Colson et al, , 2006Johnson et al, 2007). As discussed above (section V.C), estrogen receptors are located within brain nuclei that innervate the cerebral vasculature as well as other nuclei regulating cardiovascular function (Martin and Behbehani, 2006).…”

Estrogens and Brain

“…Экспериментальные животные с фенотипом CC рецептора эстрогена РЭα имеют суще-ственное увеличение риска инсульта вне зависимости от обычных факторов риска [35]. Фармакогенетические данные [36] свидетельствуют о связи полиморфизма РЭα (ESR1) с активным атеросклерозом и семейной формой мигрени (G594A экзон 8). Влияние эстрогенов на сосуды мозга в целом складывается из действия на миоциты и изменения эндотелиальной функции (жизнеспособ-ность, антиатерогенное действие, цитокинопродукция), что в конечном итоге приводит к вазодилатации и более активному ангиогенезу, снижению проницаемости гема-тоэнцефалического барьера (ГЭР), подавлению вос-палительного ответа и пролиферации миоцитов [37].…”

Migraine pathogenesis and state of pharmacological treatment options

“…A particular problem is the prediction of which patients will respond to which substance as treatment is often largely conducted by trial and error, which is frustrating for the patients and treating physicians alike. In order to obtain a better understanding of the mechanisms of the action of the available substances, phenotype-driven treatment approaches [32] as well as pharmacogenomic considerations [33], might help to overcome such issues. Moreover, newer treatment strategies, such as the use of Botulinum toxin in migraine prevention, are currently undergoing clinical trials (Table 1).…”