Acid-sensing ion channel 1: a novel therapeutic target for migraine with aura.

Objective: Migraine with aura is a severe debilitating neurological disorder with few relatively specific therapeutic options. Methods: We used amiloride, a blocker of epithelial sodium channels, to evaluate its pharmacological potential and explored the biology of a potential mechanism of action in well-established experimental models. Results: Amiloride was shown to block cortical spreading depression, the experimental correlate of aura, and inhibited trigeminal activation in in vivo migraine models, via an acid-sensing ion channel 1 mechanism. Remarkably, amiloride then demonstrated good clinical efficacy in a small open-labeled pilot study of patients, reducing aura and headache symptoms in 4 of 7 patients with otherwise intractable aura. Interpretation: The observations here identify an entirely novel treatment strategy for migraine. ANN NEUROL 2012;72:559–563