I got into contact with the research team and they confirmed that there is an ongoing study with ppms patients. The results of the preliminary study were published in the Brain journal. They think the results are encouriging. However, as the drug is off patent it will be hard to find funding for clinical trials. So, it is upto your doctor/neuro to prescribe it if sufficient supporting data emerge. I think the situation could be similar to HSCT where the treatment was approved for a different indication, but the doctors used it successfully for MS as well. Only, insurance did not cover it. With amiloride money is not a problem as it costs only a few bucks.
I am just wondering if any neuro follows this research and will use it.
Targeting ASIC1 in primary progressive multiple sclerosis: evidence of neuroprotection with amiloride
Tarunya Arun1,2,*, Valentina Tomassini1,2,3,*, Emilia Sbardella1,2,4, Michiel B. de Ruiter2,5, Lucy Matthews1,2, Maria Isabel Leite1, Rose Gelineau-Morel6, Ana Cavey1, Sandra Vergo1,7, Matt Craner1,7, Lars Fugger1,7, Alex Rovira8, Mark Jenkinson2 and Jacqueline Palace1
+ Author Affiliations
1 Division of Clinical Neurology, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK
2 Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
3 School of Medicine, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK
4 Department of Psychology, Sapienza University, Rome, Italy
5 Department of Radiology, Academic Medical Centre, University of Amsterdam, The Netherlands
6 School of Medicine, Baylor College of Medicine, Houston, TX, USA
7 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
8 Magnetic Resonance Unit, Department of Radiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
Correspondence to: Jacqueline Palace, Division of Clinical Neurology, Department of Clinical Neurosciences, Oxford University Hospitals Trust, OX3 9DU Oxford, UK, E-mail: firstname.lastname@example.org
Received July 4, 2012.
Revision received October 9, 2012.
Accepted October 20, 2012.
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 Ca2+ 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 T1-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. http://brain.oxfordjournals.org/content/136/1/106.short