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dc.contributor.authorDowling, JJ-
dc.contributor.authorMüller-Felber, W-
dc.contributor.authorSmith, BK-
dc.contributor.authorBönnemann, CG-
dc.contributor.authorKuntz, NL-
dc.contributor.authorMuntoni, F-
dc.contributor.authorServais, L-
dc.contributor.authorAlfano, LN-
dc.contributor.authorBeggs, AH-
dc.contributor.authorBilder, DA-
dc.contributor.authorBlaschek, A-
dc.contributor.authorDuong, T-
dc.contributor.authorGraham, RJ-
dc.contributor.authorJain, M-
dc.contributor.authorLawlor, MW-
dc.contributor.authorLee, J-
dc.contributor.authorCoats, J-
dc.contributor.authorLilien, C-
dc.contributor.authorLowes, LP-
dc.contributor.authorMacBean, V-
dc.contributor.authorNeuhaus, S-
dc.contributor.authorNoursalehi, M-
dc.contributor.authorPitts, T-
dc.contributor.authorFinlay, C-
dc.contributor.authorChristensen, S-
dc.contributor.authorRafferty, G-
dc.contributor.authorSeferian, AM-
dc.contributor.authorTsuchiya, E-
dc.contributor.authorJames, ES-
dc.contributor.authorMiller, W-
dc.contributor.authorSepulveda, B-
dc.contributor.authorVila, MC-
dc.contributor.authorPrasad, S-
dc.contributor.authorRico, S-
dc.contributor.authorShieh, PB-
dc.identifierTrial registration number: NCT02704273-
dc.identifier.citationDowling, J.J., Müller-Felber, W., Smith, B.K., Bönnemann, C.G., Kuntz, N.L., Muntoni, F., Servais, L., Alfano, L.N., Beggs, A.H., Bilder, D.A., Blaschek, A., Duong, T., Graham, R.J., Jain, M., Lawlor, M.W., Lee, J., Coats, J., Lilien, C., Lowes, L.P., MacBean, V., Neuhaus, S., Noursalehi, M., Pitts, T., Finlay, C., Christensen, S., Rafferty, G., Seferian, A.M., Tsuchiya, E., James, E.S., Miller, W., Sepulveda, B., Vila, M.C., Prasad, S., Rico, S. and Shieh, P.B. (2022) 'INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy', Journal of Neuromuscular Diseases, 9 (4), pp. 503 - 516 (14). doi: 10.3233/jnd-210781.en_US
dc.descriptionSupplementary Material: The supplementary material is available in the electronic version of this article:
dc.description.abstractCopyright © 2022 The authors. Background X-linked myotubular myopathy (XLMTM) is a life-threatening congenital myopathy that, in most cases, is characterized by profound muscle weakness, respiratory failure, need for mechanical ventilation and gastrostomy feeding, and early death. Objective We aimed to characterize the neuromuscular, respiratory, and extramuscular burden of XLMTM in a prospective, longitudinal study. Methods Thirty-four participants <  4 years old with XLMTM and receiving ventilator support enrolled in INCEPTUS, a prospective, multicenter, non-interventional study. Disease-related adverse events, respiratory and motor function, feeding, secretions, and quality of life were assessed. Results During median (range) follow-up of 13.0 (0.5, 32.9) months, there were 3 deaths (aspiration pneumonia; cardiopulmonary failure; hepatic hemorrhage with peliosis) and 61 serious disease-related events in 20 (59%) participants, mostly respiratory (52 events, 18 participants). Most participants (80%) required permanent invasive ventilation (>16 hours/day); 20% required non-invasive support (6–16 hours/day). Median age at tracheostomy was 3.5 months (95% CI: 2.5, 9.0). Thirty-three participants (97%) required gastrostomy. Thirty-one (91%) participants had histories of hepatic disease and/or prospectively experienced related adverse events or laboratory or imaging abnormalities. CHOP INTEND scores ranged from 19–52 (mean: 35.1). Seven participants (21%) could sit unsupported for≥30 seconds (one later lost this ability); none could pull to stand or walk with or without support. These parameters remained static over time across the INCEPTUS cohort. Conclusions INCEPTUS confirmed high medical impact, static respiratory, motor and feeding difficulties, and early death in boys with XLMTM. Hepatobiliary disease was identified as an under-recognized comorbidity. There are currently no approved disease-modifying treatments.en_US
dc.description.sponsorshipThe INCEPTUS and ASPIRO studies are sponsored by Astellas Gene Therapies.en_US
dc.format.extent503 - 516 (14)-
dc.publisherIOS Pressen_US
dc.rightsCopyright © 2022 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0).-
dc.subjectX-linked myotubular myopathyen_US
dc.subjectcentronuclear myopathyen_US
dc.subjectneuromuscular diseasesen_US
dc.subjectrespiratory failureen_US
dc.subjectmotor disordersen_US
dc.titleINCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathyen_US
dc.relation.isPartOfJournal of Neuromuscular Diseases-
dc.rights.holderThe Authors-
Appears in Collections:Dept of Health Sciences Research Papers

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