Targeting ASIC1 in primary progressive multiple sclerosis: evidence of neuroprotection with amiloride

This interesting pilot study looked at the neuroprotective effects of amiloride in patients with primary progressive MS.

Amiloride is a potassium sparing diuretic that is currently licensed for hypertension and congestive cardiac failure. Experimental models of amiloride showed neuroprotection and myeloprotective effects but had been untested on patients with MS.

A cohort of 14 patients with primary progressive MS underwent serial magnetic resonance imaging scans before and during amiloride treatment for a period of three years. The researchers also looked at acid-sensing ion channel 1 (ASIC1) expression in chronic brain lesions from post-mortem of patients with PPMS in order to look for the target process for neuroprotection.

Results showed a significant reduction in normalised annual rate of whole-brain volume during the treatment phase, compared with the pretreatment phase. Also, they showed changes in diffusion indices of tissue damage within major clinically relevant white matter and deep grey matter structures were significantly reduced during the treatment phase.

Overall, this shows the contribution of ASIC1 to neurodegeneration in MS and suggests that amiloride may exert neuroprotective effects in patients with PPMS. This pilot study supports future randomised controlled trials measuring neuroprotection with amiloride in patients with MS.

Authors: Arun T, Tomassini V, Sbardella E

Source: Brain. 2013 Jan;136(Pt 1):106-15. doi: 10.1093/brain/aws325

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