Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic–Intraosseous Administration

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2023-11-24 DOI:10.1007/s00005-023-00691-y
Adam Niezgoda, Grzegorz Biegański, Jacek Wachowiak, Jarosław Czarnota, Krzysztof Siemionow, Ahlke Heydemann, Anna Ziemiecka, Maria H. Sikorska, Katarzyna Bożyk, Maria Siemionow
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Abstract

Duchenne muscular dystrophy (DMD) is a lethal X-linked disease caused by mutations in the dystrophin gene, leading to muscle degeneration and wasting. Electromyography (EMG) is an objective electrophysiological biomarker of muscle fiber function in muscular dystrophies. A novel, DT-DEC01 therapy, consisting of Dystrophin Expressing Chimeric (DEC) cells created by fusing allogeneic myoblasts from normal donors with autologous myoblasts from DMD-affected patients, was assessed for safety and preliminary efficacy in boys of age 6–15 years old (n = 3). Assessments included EMG testing of selected muscles of upper (deltoideus, biceps brachii) and lower (rectus femoris and gastrocnemius) extremities at the screening visit and at 3, 6, and 12 months following systemic–intraosseous administration of a single low dose of DT-DEC01 therapy (Bioethics Committee approval no. 46/2019). No immunosuppression was administered. Safety of DT-DEC01 was confirmed by the lack of therapy-related Adverse Events or Serious Adverse Events up to 22 months following DT-DEC01 administration. EMG of selected muscles of both, ambulatory and non-ambulatory patients confirmed preliminary efficacy of DT-DEC01 therapy by an increase in motor unit potentials (MUP) duration, amplitudes, and polyphasic MUPs at 12 months. This study confirmed EMG as a reliable and objective biomarker of functional assessment in DMD patients after intraosseous administration of the novel DT-DEC01 therapy.

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运动单位电位持续时间作为DT-DEC01细胞治疗杜氏肌萎缩症患者全身-骨内给药后12个月疗效的生物标志物的评估
杜氏肌营养不良症(DMD)是一种致命的x连锁疾病,由肌营养不良蛋白基因突变引起,导致肌肉变性和萎缩。肌电图(Electromyography, EMG)是肌营养不良患者肌纤维功能的客观电生理生物标志物。一种新的DT-DEC01疗法,由来自正常供体的异体肌母细胞与来自dmd患者的自体肌母细胞融合产生的表达抗肌萎缩蛋白的嵌合细胞(DEC)组成,在6-15岁的男孩中评估了安全性和初步疗效(n = 3)。评估包括在筛查访问时以及在全身骨内给予单次低剂量DT-DEC01治疗后的3,6和12个月对上肢(三角肌、肱二头肌)和下肢(股直肌和腓肠肌)选定的肌肉进行肌电图测试(生物伦理委员会批准号:46/2019)。未进行免疫抑制。DT-DEC01的安全性通过在给药后22个月内无治疗相关不良事件或严重不良事件得到证实。通过运动单位电位(MUP)持续时间、振幅和12个月时多相MUPs的增加,对门诊和非门诊患者选定肌肉的肌电图证实了DT-DEC01治疗的初步疗效。本研究证实肌电图是骨内给药新型DT-DEC01治疗后DMD患者功能评估的可靠和客观的生物标志物。
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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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