Amiloride, Fluoxetine, Riluzole Do Not Reduce Atrophy Rates in Secondary Progressive MS

The following article is part of conference coverage from the 8th Joint American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) MSVirtual2020 event. Neurology Advisor‘s staff will be reporting breaking news associated with research conducted by leading experts in neurology. .

In individuals with secondary progressive multiple sclerosis (MS), amiloride, fluoxetine, and rizuole treatments, do not translate into a long-term reduction in atrophy rates, according to study results presented at the 8th Joint American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) MSVirtual2020 event, held September 11-13, 2020.

In this study, researchers sought to investigate the effects of amiloride on total N-acetyl aspartate plus N-acetyl aspartyl glutamate (tNAA) levels, the effects of fluoxetine on tNAA and myoinositol levels, and those of riluzole on glutamate plus glutamine levels. They accomplished this using proton magnetic resonance spectroscopic imaging (MRSI) data at baseline and 96 weeks.

The investigators recruited 108 participants from the MS-SMART trial (ClinicalTrials.gov Identifier: NCT01910259), a phase 2b, randomized, multiarm study that compared the neuroprotective effects of amiloride, fluoxetine, and riluzole to placebo in patients with secondary progressive MS, and used MRSI to obtain brain metabolic data for participants at baseline and 96 weeks.  The participants in the current study had chemical shift imaging in a single slice of the brain at 3T done. Study researchers calculated metabolite levels and ratios to creatine for gray matter and normal appearing white matter. Additionally they utilized multiple regression models that accounted for sex, age, and baseline Expanded Disability Status Scale.

In the fluoxetine arm, changes in tNAA levels observed in normal appearing white matter or gray matter were not significant; however, the ratio of myoinositol to creatine in normal appearing white matter (but not gray matter) was lower at 96 weeks in the intervention group (β=-0.21; 95% CI, -0.40 to -0.02; P =.03). In the riluzole arm, study researchers observed reductions in glutamate plus glutamine in gray matter (β=-0.25; 95% CI, -0.47 to -0.04; P =.02) and reductions in the ratio of glutamate plus glutamine to creatine (β=-0.29; 95% CI, -0.50 to -0.08; P =.007), but no changes were observed in normal appearing white matter. No change in tNAA levels was observed in normal appearing white matter or gray matter among the participants in the amiloride arm.

Neither amiloride nor fluoxetine had any effect on tNAA levels in normal appearing white matter or gray matter; however, fluoxetine displayed a reduction in the myoinositol to creatine ratio in normal appearing white matter, suggesting a decrease in astrogliosis. Additionally, riluzole reduced glutamate plus glutamine levels in gray matter. Overall, however, the study researchers concluded that the tested “interventions did not translate into a reduction in atrophy rate” among patients with secondary progressive MS.

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Reference

John N, Solanky B, De Angelis F, et al. The effects of amiloride, fluoxetine and riluzole over 96 weeks on metabolic markers of brain injury in secondary progressive multiple sclerosis. Presented at: 8^th Joint American Committee for Treatment and Research in Multiple Sclerosis and European Committee for Treatment and Research in Multiple Sclerosis MSVirtual2020 event; September 11-13, 2020; Abstract P0651.