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Posted: Sat Oct 11, 2008 11:11 am Post subject: Flupirtine
Flupirtine is an approved oral pain medication that is in phase 2 trials in MS. This is an interesting abstract.
Flupirtine as Neuroprotective Add-On Therapy in Autoimmune Optic Neuritis.
Am J Pathol. 2008 Oct 2.
Sättler MB, Williams SK, Neusch C, Otto M, Pehlke JR, Bähr M, Diem R.
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 of the central nervous system that results in persistent impairment in young adults. During chronic progressive disease stages, there is a strong correlation between neurodegeneration and disability. Current therapies fail to prevent progression of neurological impairment during these disease stages.
Flupirtine, a drug approved for oral use in patients suffering from chronic pain, was used in a rat model of autoimmune optic neuritis and significantly increased the survival of retinal ganglion cells, the neurons that form the axons of the optic nerve. When flupirtine was combined with interferon-beta, an established immunomodulatory therapy for MS, visual functions of the animals were improved during the acute phase of optic neuritis. Furthermore, flupirtine protected retinal ganglion cells from degeneration in a noninflammatory animal model of optic nerve transection.
Although flupirtine was shown previously to increase neuronal survival by Bcl-2 up-regulation, this mechanism does not appear to play a role in flupirtine-mediated protection of retinal ganglion cells either in vitro or in vivo. Instead, we showed through patch-clamp investigations that the activation of inwardly rectifying potassium channels is involved in flupirtine-mediated neuroprotection. Considering the few side effects reported in patients who receive long-term flupirtine treatment for chronic pain, our results indicate that this drug is an interesting candidate for further evaluation of its neuroprotective potential in MS.
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