title: Development of dalfampridine, a novel pharmacologic approach for treating walking impairment in multiple sclerosis.
abstract: Walking impairment is a clinical hallmark of multiple sclerosis (MS). Dalfampridine-ER, an extended-release formulation of dalfampridine (also known by its chemical name, 4-aminopyridine, and its international nonproprietary name, fampridine), was developed to maintain drug plasma levels within a narrow therapeutic window, and assessed for its ability to improve walking in MS. The putative mechanism of action of dalfampridine-ER is restoration of axonal conduction via blockade of the potassium channels that become exposed during axonal demyelination. Two pivotal phase III clinical trials demonstrated that dalfampridine-ER 10-mg tablets administered twice daily improved walking speed and patient-reported perceptions of walking in some patients. Dalfampridine-ER was generally well tolerated, and, at the approved dose, risk of seizure was neither elevated relative to placebo nor higher than the rate in the MS population. Dalfampridine-ER (AMPYRA®) was approved in the United States for the treatment of walking in patients with MS as demonstrated by an increase in walking speed. The use of the dalfampridine-ER is contraindicated in patients with a history of seizure. It is the first pharmacologic therapy for this indication and has been incorporated into clinical management of MS.
authors.affiliation: Acorda Therapeutics, Ardsley, New York.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Blight
authors.forename: Herbert R
authors.initials: HR
authors.lastname: Henney
authors.forename: Ron
authors.initials: R
authors.lastname: Cohen
mesh_terms: D015761:4-Aminopyridine / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000639:trends; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D026902:Potassium Channel Blockers / Q000627:therapeutic use*; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology*
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine
keywords: 4-aminopyridine; dalfampridine; fampridine; multiple sclerosis; walking