دورية أكاديمية
INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy.
| العنوان: | INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy. |
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| المؤلفون: | Dowling, James J, Müller-Felber, Wolfgang, Smith, Barbara K, Bönnemann, Carsten G, Kuntz, Nancy L, Muntoni, Francesco, Servais, Laurent, Alfano, Lindsay N, Beggs, Alan H, Bilder, Deborah A, Blaschek, Astrid, Duong, Tina, Graham, Robert J, Jain, Minal, Lawlor, Michael W, Lee, Jun, Coats, Julie, Lilien, Charlotte, Lowes, Linda P, MacBean, Victoria, Neuhaus, Sarah, Noursalehi, Mojtaba, Pitts, Teresa, Finlay, Caroline, Christensen, Sarah, Rafferty, Gerrard, Seferian, Andreea M, Tsuchiya, Etsuko, James, Emma S, Miller, Weston, Sepulveda, Bryan, Vila, Maria Candida, Prasad, Suyash, Rico, Salvador, Shieh, Perry B, INCEPTUS investigators |
| المصدر: | Journal of Neuromuscular Diseases, 9 (4), 503-516 (2022) |
| بيانات النشر: | IOS Press BV, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | X-linked myotubular myopathy, centronuclear myopathy, mechanical, motor disorders, neuromuscular diseases, respiratory failure, ventilators, Child, Preschool, Genetic Therapy, Humans, Longitudinal Studies, Male, Prospective Studies, Myopathies, Structural, Congenital/genetics, Myopathies, Structural, Congenital/therapy, Quality of Life, Myopathies, Structural, Congenital, Neurology, Neurology (clinical), Human health sciences, Pediatrics, Sciences de la santé humaine, Neurologie, Pédiatrie |
| الوصف: | 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. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501Test article peer reviewed |
| اللغة: | English |
| العلاقة: | https://content.iospress.com/download?id=10.3233/JND-210781Test; urn:issn:2214-3599; urn:issn:2214-3602 |
| DOI: | 10.3233/JND-210781 |
| الوصول الحر: | https://orbi.uliege.be/handle/2268/295915Test |
| حقوق: | open access http://purl.org/coar/access_right/c_abf2Test info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsorb.295915 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.3233/JND-210781 |
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