An algorithm for discontinuing mechanical ventilation in boys with x-linked myotubular myopathy after positive response to gene therapy: the ASPIRO experience.

Autor: Graham RJ; Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Amin R; Hospital for Sick Children, University of Toronto, Toronto, ON, Canada., Demirel N; Mayo Clinic, Rochester, MN, USA., Edel L; Great Ormond Street Hospital for Children London, London, UK., Lilien C; MDUK Oxford Neuromuscular Centre, Oxford, UK.; Institute I-Motion, Hôpital Armand Trousseau, Paris, France., MacBean V; Brunel University London, London, UK., Rafferty GF; King's College London, London, UK., Sawnani H; Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.; University of Cincinnati, Cincinnati College of Medicine, Cincinnati, OH, USA., Schön C; Hauner's Children's Hospital, University of Munich, Munich, Germany., Smith BK; University of Florida, Gainesville, FL, USA., Syed F; Hospital for Sick Children, University of Toronto, Toronto, ON, Canada., Sarazen M; Formerly of Astellas Gene Therapies, San Francisco, CA, USA., Prasad S; Formerly of Astellas Gene Therapies, San Francisco, CA, USA., Rico S; Formerly of Astellas Gene Therapies, San Francisco, CA, USA., Perez GF; Oishei Children's Hospital, Jacobs School of Medicine and Biomedical Sciences, Oishei Children's Hospital University at Buffalo, Buffalo, NY, USA. gperez@upa.chob.edu.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2024 Sep 16; Vol. 25 (1), pp. 342. Date of Electronic Publication: 2024 Sep 16.
DOI: 10.1186/s12931-024-02966-0
Abstrakt: X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy. Most (80%) children with XLMTM have profound muscle weakness and hypotonia at birth resulting in severe respiratory insufficiency, the inability to sit up, stand or walk, and early mortality. At birth, 85-90% of children with XLMTM require mechanical ventilation, with more than half requiring invasive ventilator support. Historically, ventilator-dependent children with neuromuscular-derived respiratory failure of this degree and nature, static or progressive, are not expected to achieve complete independence from mechanical ventilator support. In the ASPIRO clinical trial (NCT03199469), participants receiving a single intravenous dose of an investigational gene therapy (resamirigene bilparvovec) started showing significant improvements in daily hours of ventilation support compared with controls by 24 weeks post-dosing, and 16 of 24 dosed participants achieved ventilator independence between 14 and 97 weeks after dosing. At the time, there was no precedent or published guidance for weaning chronically ventilated children with congenital neuromuscular diseases off mechanical ventilation. When the first ASPIRO participants started showing dramatically improved respiratory function, the investigators initiated efforts to safely wean them off ventilator support, in parallel with primary protocol respiratory outcome measures. A group of experts in respiratory care and physiology and management of children with XLMTM developed an algorithm to safely wean children in the ASPIRO trial off mechanical ventilation as their respiratory muscle strength increased. The algorithm developed for this trial provides recommendations for assessing weaning readiness, a stepwise approach to weaning, and monitoring of children during and after the weaning process.
(© 2024. The Author(s).)
Databáze: MEDLINE
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