amiloride hydrochlorothiazide as treatment of acute inflammation of the optic nerve

Conditions: Optic; Neuritis, With Demyelination

Summary: following acute inflammation of the optic nerve region, as commonly seen in multiple sclerosis patients, the optic nerve often undergoes atrophy, thus representing permanent damage. data from animal studies suggest that amiloride may prevent this process. the aim of this study is to assess a potential neuroprotective effect of amiloride in acute autoimmune inflammation of the optic nerve region.

recent studies have shown that the acid-sensing ion channel 1 (asic1) contributes to the axonal degeneration in cns lesions physiologically, asic1 has been described as a postsynaptic proton receptor on hippocampal neurons influencing the intracellular ca2+ concentration. in ms, asic1 seems to activate under acidic conditions predominating in the inflammatory cns lesions leading to a na+ and ca2+ overload and consecutive damage and apoptosis of axons. consecutively, in a ms mousemodel axonal damage was significantly less pronounced after administering amiloride, a clinically safe blocker of asics. so asic1 seems to play a major role in axonal degeneration in ms. to our knowledge no clinical studies have tested those promising in vitro results in humans so far. only one retrospective registry-based cohort study was performed. this study showed no difference in the risk of incident ms or hospitalization and death among ms patients using amilorid compared to those using thiazide diuretics. however, this study has numerous limitations with respect to it's retrospective designone and the fact that amilorid users were at the vast majority older individuals. such a late stage of the ms course does not seem to be the best window of opportunity for interventions with neuroprotective agents. moreover, death may be a too multifactorial parameter to correspond with axonal damage alone. consequently, a more sensitive parameter for axonal damage in ms is needed to test the impact of amiloride on neuroprotection and repair.based on the findings described above we intend to assess the potential neuroprotective effect of amiloride hydrochlorothiazide (amilostad hct®) in patients with optic neuritis (on), which has already been demonstrated in a mouse model. on is one of the most common manifestations of ms and has already been proven appropiate to test neuroprotective agents.

Eligibility criteria:
inclusion criteria: patients between 18 and 50 years of age with a first episode of optic neuritis (on) and a visual acuity decreased to \<0,6 will be eligible for inclusion in the study. diagnosis of on has to be confirmed by an ophthalmologist. onset of symptoms has to be within 10 days prior to inclusion into the study exclusion criteria: * known allergy or hypersensitivity to amilostad hct or any of its ingredients * known allergy or hypersensitivity to other sulphonamide-derived drugs * impaired renal function or any known renal disease * intake of other potassium-conserving diuretics * intake of potassium supplements or a special potassium rich diet * intake of spironolactone or triamterene * moderate to severe hepatic failure * morbus addison * known hypercalcaemia * intake of lithium therapy * blood urea \> 10mmol/l * diabetes mellitus * history of on or any other ocular disease (affected as well as unaffected eye) * pregnancy or lactation period * treatment with corticosteroids or amiloride within 30 days prior to the inclusion into the study * use of any immunomodulatory or immunosuppressive agents anytime in the past * dearrangement of serum sodium or potassium levels on the lab