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.