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dc.contributor.authorAhmed, Mhoriam
dc.contributor.authorMachado, Pedro M.
dc.contributor.authorMiller, Adrian
dc.contributor.authorSpicer, Charlotte
dc.contributor.authorHerbelin, Laura
dc.contributor.authorHe, Jianghua
dc.contributor.authorNoel-MacDonnell, Janelle Rose
dc.contributor.authorWang, Yunxia
dc.contributor.authorMcVey, April L.
dc.contributor.authorPasnoor, Mamatha
dc.contributor.authorGallagher, Philip M.
dc.contributor.authorStatland, Jeffrey
dc.contributor.authorLu, Ching-Hua
dc.contributor.authorKalmar, Bernadett
dc.contributor.authorBrady, Stefen
dc.contributor.authorSethi, Huma
dc.contributor.authorSamandouras, George
dc.contributor.authorParton, Matt
dc.contributor.authorHolton, Janice L.
dc.contributor.authorWeston, Anne
dc.contributor.authorCollinson, Lucy
dc.contributor.authorTaylor, J. Paul
dc.contributor.authorSchiavo, Giampietro
dc.contributor.authorHanna, Michael G.
dc.contributor.authorBarohn, Richard J.
dc.contributor.authorDimachkie, Mazen M.
dc.contributor.authorGreensmith, Linda
dc.identifier.citationMhoriam Ahmed, Pedro M. Machado, Adrian Miller, Charlotte Spicer, Laura Herbelin, Jianghua He, Janelle Noel, Yunxia Wang, April L. McVey, Mamatha Pasnoor, Philip Gallagher, Jeffrey Statland, Ching-Hua Lu, Bernadett Kalmar, Stefen Brady, Huma Sethi, George Samandouras, Matt Parton, Janice L. Holton, Anne Weston, Lucy Collinson, J. Paul Taylor, Giampietro Schiavo, Michael G. Hanna, Richard J. Barohn, Mazen M. Dimachkie, Linda Greensmith Sci Transl Med. Author manuscript; available in PMC 2016 Sep 30. Published in final edited form as: Sci Transl Med. 2016 Mar 23; 8(331): 331ra41. doi: 10.1126/scitranslmed.aad4583en_US
dc.description.abstractSporadic inclusion body myositis (sIBM) is the commonest severe myopathy in patients over age 50. Previous therapeutic trials have targeted the inflammatory features of sIBM, but all have failed. Since protein dyshomeostasis may also play a role in sIBM, we tested the effects of targeting this feature of the disease. Using rat myoblast cultures, we found that up-regulation of the heat shock response with Arimoclomol reduced key pathological markers of sIBM in vitro. Furthermore, in mutant valosin-containing protein VCP mice, which develop an inclusion body myopathy (IBM), treatment with Arimoclomol ameliorated disease pathology and improved muscle function. We therefore evaluated the safety and tolerability of Arimoclomol in an investigator-lead, randomised, double-blind, placebo-controlled, proof-of-concept patient trial and gathered exploratory efficacy data which showed that Arimoclomol was safe and well tolerated. Although Arimoclomol improved some IBM-like pathology in vitro and in vivo in the mutant VCP mouse, we did not see statistically significant evidence of efficacy in this proof of concept patient trial.en_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.titleTargeting Protein Homeostasis in Sporadic Inclusion Body Myositisen_US
kusw.kuauthorGallagher, Philip
kusw.kudepartmentHealth, Sport & Exercise Scienceen_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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