4-Aminopyridine ameliorates mobility but not disease course in an animal model of multiple sclerosis

Kerstin Goebel*, Jan-Hendrik Wedell, Alexander M. Herrmann, Lydia Wachsmuth, Susann Pankratz, Stefan Bittner, Thomas Budde, Christoph Kleinschnitz, Cornelius Faber, Heinz Wiendl, Sven G. Meuth*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Neuropathological changes following demyelination in multiple sclerosis (MS) lead to a reorganization of axolemmal channels that causes conduction changes including conduction failure. Pharmacological modulation of voltage-sensitive potassium channels (K(V)) has been found to improve conduction in experimentally induced demyelination and produces symptomatic improvement in MS patients. Here we used an animal model of autoimmune inflammatory neurodegeneration, namely experimental autoimmune encephalomyelitis (EAE), to test the influence of the K(V)-inhibitor 4-aminopyridine (4-AP) on various disease and immune parameters as well as mobility in MOG? immunized C57Bl/6 mice. We challenged the hypothesis that 4-AP exerts relevant immunomodulatory or neuroprotective properties. Neither prophylactic nor therapeutic treatment with 4-AP altered disease incidence or disease course of EAE. Histopathological signs of demyelination and neuronal damage as well as MRI imaging of brain volume changes were unaltered. While application of 4-AP significantly reduced the standing outward current of stimulated CD4(+) T cells compared to controls, it failed to impact intracellular calcium concentrations in these cells. Compatibly, KV channel inhibition neither influenced CD4(+) T cell effector functions (proliferation, IL17 or IFN? production). Importantly however, despite equal disease severity scores 4-AP treated animals showed improved mobility as assessed by 2 independent methods, 1) foot print and 2) rotarod analysis (0.332 ? 0.03, n=7 versus 0.399 ? 0.08, n=14, p
Original languageEnglish
Pages (from-to)62-71
JournalExperimental Neurology
Publication statusPublished - Oct 2013


  • 4-Aminopyridine
  • Multiple sclerosis
  • EAE
  • Symptomatic treatment
  • Mobility

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