Saturday, 23 November 2013

Drug may work in PPMS

#MS Research Drug working for PPMS

Arun T, Tomassini V, Sbardella E, de Ruiter MB, Matthews L, Leite MI, Gelineau-Morel R, Cavey A, Vergo S, Craner M, Fugger L, Rovira A, Jenkinson M, Palace J. Targeting ASIC1 in primary progressive multiple sclerosis: evidence of neuroprotection with amiloride. Brain. 2013;136(Pt 1):106-15. 

Neurodegeneration is the main cause for permanent disability in multiple sclerosis. The effect of current immunomodulatory treatments on neurodegeneration is insufficient. Therefore, direct neuroprotection and myeloprotection remain an important therapeutic goal. Targeting acid-sensing ion channel 1 (encoded by the ASIC1 gene), which contributes to the excessive intracellular accumulation of injurious Na(+) and Ca(2+) and is over-expressed in acute multiple sclerosis lesions, appears to be a viable strategy to limit cellular injury that is the substrate of neurodegeneration. While blockade of ASIC1 through amiloride, a potassium sparing diuretic that is currently licensed for hypertension and congestive cardiac failure, showed neuroprotective and myeloprotective effects in experimental models of multiple sclerosis, this strategy remains untested in patients with multiple sclerosis. In this translational study, we tested the neuroprotective effects of amiloride in patients with primary progressive multiple sclerosis. First, we assessed ASIC1 expression in chronic brain lesions from post-mortem of patients with progressive multiple sclerosis to identify the target process for neuroprotection. Second, we tested the neuroprotective effect of amiloride in a cohort of 14 patients with primary progressive multiple sclerosis using magnetic resonance imaging markers of neurodegeneration as outcome measures of neuroprotection. Patients with primary progressive multiple sclerosis underwent serial magnetic resonance imaging scans before (pretreatment phase) and during (treatment phase) amiloride treatment for a period of 3 years. Whole-brain volume and tissue integrity were measured with high-resolution T(1)-weighted and diffusion tensor imaging. In chronic brain lesions of patients with progressive multiple sclerosis, we demonstrate an increased expression of ASIC1 in axons and an association with injury markers within chronic inactive lesions. In patients with primary progressive multiple sclerosis, we observed a significant reduction in normalized annual rate of whole-brain volume during the treatment phase, compared with the pretreatment phase (P = 0.018, corrected). Consistent with this reduction, we showed that changes in diffusion indices of tissue damage within major clinically relevant white matter (corpus callosum and corticospinal tract) and deep grey matter (thalamus) structures were significantly reduced during the treatment phase (P = 0.02, corrected). Our results extend evidence of the contribution of ASIC1 to neurodegeneration in multiple sclerosis and suggest that amiloride may exert neuroprotective effects in patients with progressive multiple sclerosis. This pilot study is the first translational study on neuroprotection targeting ASIC1 and supports future randomized controlled trials measuring neuroprotection with amiloride in patients with multiple sclerosis.
When getting good news for RRMS, it usually means there is nothing to cheer for people with PPMS. Now I may have posted on this before but can't remember doing it, but as the search function was not working, I decided I will post on this. 

Based on studies in Animals, it was suggested that an ion channel blocker that works on Acid Sensing Ion Channel (ASIC) was neuroprotective. This was work that hailed from Oxford.

So then they moved on to humans and in this study they did a before and after in PPMS and treating with an ASIC blocker called Amiloride, which worked in the animals to save nerves. This study suggests it may have neuroprotective effects in MS. Next they need to do a controlled trial. However, as I think I forgot to post on this..things have moved on. The Oxford group have got a trial funded by UK MS Society ongoing treating optic neuritis (NCT01802489) and there is another UK wide in secondary progressive MS (NCT01910259) funded by NIHR, MRC, UK MS Society etc Check out Clin Trials. gov for treatment options in an area near you.

CoI:None Relevant

3 comments:

  1. Targeting ASIC1 in primary progressive multiple sclerosis: evidence of neuroprotection with amiloride.http://www.ncbi.nlm.nih.gov/m/pubmed/23365093

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  2. The trouble with Amiloride is that it tends to worsen nerve conduction so one's walking might feel a whole lot worse on it than not...

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  3. They are only studying this drug in SPMS. Why not PPMS?!
    Also,if you have nothing to give PPMS people,why not give them something that could perhaps help? Why wait for a clinical trial-that probably won't happen-before our Neuros have the courage to prescribe it? Dr's prescribe off-label all the time,unless of course you have PPMS. At which point you are on your own. An untoucheable.

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