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Enhancing Neural Transmission in Multiple Sclerosis (4-Aminopyridine Therapy)

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Neurotherapeutics

Abstract

Enhancing neural transmission by improving axonal conduction and synaptic neurotransmitter release is a novel strategy to improve symptoms in multiple sclerosis. Dalfampridine (4-aminopyridine extended-release) is a first-in-class medication that targets the damaged nervous system through blockage of voltage-gated potassium channels. Through a series of clinical trials, dalfampridine (dosed at 10 mg twice daily) has been found to improve walking speed by approximately 25 % on average in one third of individuals with multiple sclerosis regardless of disease stage. Furthermore, it significantly improves patients' perception of their ambulatory disability and may improve lower extremity strength. Given the mechanism of action, the most serious adverse effect is its pro-convulsant property, which occurs more frequently at high serum concentrations. The most common adverse events include increased falls, urinary tract infections, dizziness, insomnia, and headaches. Despite these potential side-effects, the vast majority of individuals who derive benefit continue on the treatment. The exact mechanism of action is uncertain, as is the reason for response variability. The medication serves as proof-of-concept that targeting axonal transmission can improve disability in multiple sclerosis.

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Authors and Affiliations

  1. Department of Neurology, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Andrew D. Goodman & Robert Thompson Stone

  2. Division Child Neurology, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Robert Thompson Stone

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  1. Andrew D. Goodman
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  2. Robert Thompson Stone
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Correspondence to Andrew D. Goodman.

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Goodman, A.D., Stone, R.T. Enhancing Neural Transmission in Multiple Sclerosis (4-Aminopyridine Therapy). Neurotherapeutics 10, 106–110 (2013). https://doi.org/10.1007/s13311-012-0156-3

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