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

Philip R. Holland; Simon Akerman; Anna P. Andreou; Nazia Karsan; John A. Wemmie; Peter J. Goadsby

doi:10.1002/ana.23653

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

Philip R. Holland
, Simon Akerman
, Anna P. Andreou
, Nazia Karsan
, John A. Wemmie
, Peter J. Goadsby^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

101 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	559-563
Number of pages	5
Journal	Annals of Neurology
Volume	72
Issue number	4
DOIs	https://doi.org/10.1002/ana.23653
Publication status	Published - Oct 2012

Keywords

CORTICAL SPREADING DEPRESSION
CONTRIBUTES
SYSTEM

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10.1002/ana.23653

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title = "Acid-sensing ion channel 1: A novel therapeutic target for migraine with aura",

abstract = "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. ",

keywords = "CORTICAL SPREADING DEPRESSION, CONTRIBUTES, SYSTEM",

author = "Holland, \{Philip R.\} and Simon Akerman and Andreou, \{Anna P.\} and Nazia Karsan and Wemmie, \{John A.\} and Goadsby, \{Peter J.\}",

year = "2012",

month = oct,

doi = "10.1002/ana.23653",

language = "English",

volume = "72",

pages = "559--563",

journal = "Annals of Neurology",

issn = "0364-5134",

publisher = "John Wiley \& Sons Inc.",

number = "4",

}

TY - JOUR

T1 - Acid-sensing ion channel 1

T2 - A novel therapeutic target for migraine with aura

AU - Holland, Philip R.

AU - Akerman, Simon

AU - Andreou, Anna P.

AU - Karsan, Nazia

AU - Wemmie, John A.

AU - Goadsby, Peter J.

PY - 2012/10

Y1 - 2012/10

N2 - 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.

AB - 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.

KW - CORTICAL SPREADING DEPRESSION

KW - CONTRIBUTES

KW - SYSTEM

U2 - 10.1002/ana.23653

DO - 10.1002/ana.23653

M3 - Article

SN - 0364-5134

VL - 72

SP - 559

EP - 563

JO - Annals of Neurology

JF - Annals of Neurology

IS - 4

ER -

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

Abstract

Keywords

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