Flupirtine as Neuroprotective Add-On Therapy in Autoimmune Optic Neuritis

Muriel B. Sättler^*, Sarah K. Williams, Clemens Neusch^*, Markus Otto, Jens R. Pehlke, Mathias Bähr^* and Ricarda Diem

From the Department of Neurology,^* University of Göttingen, Göttingen; the Department of Neurology, University of Homburg/Saar, Homburg/Saar; and the Department of Neurology, University of Ulm, Ulm, Germany

Multiple sclerosis (MS) is a common inflammatory disease ofthe central nervous system that results in persistent impairmentin young adults. During chronic progressive disease stages,there is a strong correlation between neurodegeneration anddisability. Current therapies fail to prevent progression ofneurological impairment during these disease stages. Flupirtine,a drug approved for oral use in patients suffering from chronicpain, was used in a rat model of autoimmune optic neuritis andsignificantly increased the survival of retinal ganglion cells,the neurons that form the axons of the optic nerve. When flupirtinewas combined with interferon-β, an established immunomodulatorytherapy for MS, visual functions of the animals were improvedduring the acute phase of optic neuritis. Furthermore, flupirtineprotected retinal ganglion cells from degeneration in a noninflammatoryanimal model of optic nerve transection. Although flupirtinewas shown previously to increase neuronal survival by Bcl-2up-regulation, this mechanism does not appear to play a rolein flupirtine-mediated protection of retinal ganglion cellseither in vitro or in vivo. Instead, we showed through patch-clampinvestigations that the activation of inwardly rectifying potassiumchannels is involved in flupirtine-mediated neuroprotection.Considering the few side effects reported in patients who receivelong-term flupirtine treatment for chronic pain, our resultsindicate that this drug is an interesting candidate for furtherevaluation of its neuroprotective potential in MS.