サイトウ　カヨコ   Saitou Kayoko   齋藤　加代子    所属   医学部 医学科（東京女子医科大学病院）    職種   特任教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy.
掲載誌名	正式名：Muscle & nerve 略　 称：Muscle Nerve ISSNコード：10974598/0148639X
掲載区分	国外
巻・号・頁	pp.1-15
著者・共著者	Kichula Elizabeth A†, Proud Crystal M, Farrar Michelle A, Kwon Jennifer M, Saito Kayoko, Desguerre Isabelle, McMillan Hugh J*
発行年月	2021/06
概要	Spinal muscular atrophy (SMA) is an autosomal recessive, neurodegenerative disease caused by biallelic mutations in the survival motor neuron 1 (SMN1) gene. SMA is characterized by motor neuron degeneration, resulting in progressive muscle atrophy and weakness. Before the emergence of disease-modifying therapies, children with the most severe form of SMA would never achieve the ability to sit independently. Only 8% survived beyond 20 months of age without permanent ventilator support. One such therapy, onasemnogene abeparvovec, an adeno-associated virus-based gene replacement therapy, delivers functional human SMN through a one-time intravenous infusion. In addition to substantially improving survival, onasemnogene abeparvovec was found to increase motor milestone attainment and reduce the need for respiratory or nutritional support in many patients. This expert opinion provides recommendations and practical considerations on the patient-centered decisions to use onasemnogene abeparvovec. Recommendations include the need for patient-centered multidisciplinary care and patient selection to identify those with underlying medical conditions or active infections to reduce risks. We also describe the importance of retesting patients with elevated anti-adeno-associated virus serotype 9 antibodies. Recommendations for prednisolone tapering and monitoring for potential adverse events, including hepatotoxicity and thrombotic microangiopathy, are described. The need for caregiver education on managing day-to-day care at time of treatment and patient- and family-centered discussions on realistic expectations are also recommended. We detail the importance of following standard-of-care guidance and long-term monitoring of all children with SMA who have received one or more disease-modifying therapy using registries. We also highlight the need for presymptomatic or early symptomatic treatment of this disorder.
DOI	10.1002/mus.27363
PMID	34196026