A board to discuss future MS therapies in early stage (Phase I or II) trials.

Re: Amiloride

Postby gibbledygook » Mon Sep 02, 2013 4:38 am

Well, I took amiloride again with a dose of just 5mg and used alcohol on every night to control the night spasms. I tried it for just 3 nights and it immediately made my walking worse. Now I am also on beta interferon 1a and minocycline. I discussed amiloride with my neurologist who ran the trials for similar sodium channel blockers (lamotrigine) and a lot of the patients had similar problems but the data on those who continued taking the drug was positive. Yet because so many patients did not continue taking the drug in the trial the trial data on lamotrigine looks bad. Of course this is highly anecdotal.

J Neurol. 2012 Mar;259(3):505-14. doi: 10.1007/s00415-011-6212-9. Epub 2011 Sep 9.
Longitudinal changes in magnetisation transfer ratio in secondary progressive multiple sclerosis: data from a randomised placebo controlled trial of lamotrigine.
Hayton T, Furby J, Smith KJ, Altmann DR, Brenner R, Chataway J, Hunter K, Tozer DJ, Miller DH, Kapoor R.
Department of Neuroinflammation, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Sodium blockade with lamotrigine is neuroprotective in animal models of central nervous system demyelination. This study evaluated the effect of lamotrigine on magnetisation transfer ratio (MTR), a putative magnetic resonance imaging measure of intact brain tissue, in a group of subjects with secondary progressive multiple sclerosis (MS). In addition, the utility of MTR measures for detecting change in clinically relevant pathology was evaluated. One hundred seventeen people attending the National Hospital for Neurology and Neurosurgery or the Royal Free Hospital, London, UK, were recruited into a double-blind, parallel-group trial. Subjects were randomly assigned by minimisation to receive lamotrigine (target dose 400 mg/day) or placebo for 2 years. Treating and assessing physicians and patients were masked to treatment allocation. Results of the primary endpoint, central cerebral volume, have been published elsewhere. Significant differences between the verum and placebo arms were seen in only two measures [normal appearing grey matter (NAGM) p = 0.036 and lesion peak height (PH) p = 0.004], and in both cases there was a greater reduction in MTR in the verum arm. Significant correlations were found of change in MS functional composite with all MTR measures except lesion and normal appearing white matter (NAWM) PH. However, the change in MTR measures over 2 years were small, with only NAGM mean (p = 0.001), lesion peak location (p = 0.11) and mean (p < 0.0001) changing significantly from baseline. These data did not show that lamotrigine was neuroprotective. The clinical correlation of MTR measures was consistent, but the responsiveness to change was limited. But if I didn't suffer worse walking on this drug I would definitely try to take it.

However each time I have tried amiloride either on alcohol or gabapentin to control nights spasms my walking has deteriorated so unfortunately I'm going to try to get on fampridine instead.
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,
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