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CNS Drugs

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Restoring Axonal Function with 4-Aminopyridine: Clinical Efficacy in Multiple Sclerosis and Beyond

Review Article
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Abstract

The oral potassium channel blocker 4-aminopyridine has been used in various neurological conditions for decades. Numerous case reports and studies have supported its clinical efficacy in ameliorating the clinical presentation of certain neurological disorders. However, its short half-life, erratic drug levels, and safety-related dose restrictions limited its use as a self-compounded drug in clinical practice. This changed with the introduction of a prolonged-release formulation, which was successfully tested in patients with multiple sclerosis. It was fully approved by the US FDA in January 2010 but initially received only conditional approval from the European Medicines Agency (EMA) in July 2011. After additional clinical studies, this conditional approval was changed to unrestricted approval in August 2017. This article reviews and discusses these recent studies and places aminopyridines and their clinical utility into the context of a broader spectrum of neurological disorders, where clinical efficacy has been suggested. In 2010, prolonged-release 4-aminopyridine became the first drug specifically licensed to improve walking in patients with multiple sclerosis. About one-third of patients across disease courses benefit from this treatment. In addition, various reports indicate clinical efficacy beyond multiple sclerosis, which may broaden its use in clinical practice.

Notes

Acknowledgements

The authors thank Dr. Peter Göttle for help in creating the figures and Dr. Bernd C. Kieseier for critical review and discussion.

Compliance with Ethical Standards

Funding

The authors received no funding for writing this manuscript.

Conflict of interest

VL has received fees for speaking from Biogen, Genzyme, and Novartis and research support from Novartis. XM has received fees for consulting, serving on steering committees, and speaking at symposia from Almirall, Bayer, Biogen, Genzyme, Merck, Roche, Receptos, Sanofi, and Teva. HPH has received, with approval from the Rector of Heinrich-Heine-University, fees for consulting, serving on steering and data monitoring committees, and speaking at scientific symposia from BayerHealthcare, Biogen, Geneuro, Genzyme, Merck, Novartis, Octapharma, Receptos Celgene, Roche, Sanofi, and Teva. None of these were related to the present work.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurology, Medical FacultyHeinrich-Heine UniversityDüsseldorfGermany
  2. 2.Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (Cemcat)Hospital Universitario Vall d’HebronBarcelonaSpain
  3. 3.St. Michael’s HospitalUniversity of TorontoTorontoCanada

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