PDF(Pubmed)
Abstract：
BACKGROUND: SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness.
METHODS: LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient\'s age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed.
CONCLUSIONS: Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up.
CONCLUSIONS: Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD.
BACKGROUND: This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017-3911) and is registered at ClinicalTrial.gov ( NCT04478981 ).
METHODS: LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient\'s age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed.
CONCLUSIONS: Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up.
CONCLUSIONS: Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD.
BACKGROUND: This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017-3911) and is registered at ClinicalTrial.gov ( NCT04478981 ).
摘要：
背景：SELENON（SEPN1）相关肌病（SELENON-RM）是一种罕见的先天性肌病，其特征是缓慢进展的近端肌无力，早发性脊柱僵硬和呼吸功能不全。由LAMA2基因突变引起的肌营养不良（LAMA2相关的肌营养不良，LAMA2-MD）具有相似的临床表型，无论是严重的，由于完全层粘连蛋白亚基α2缺乏（美罗素缺乏型先天性肌营养不良1A（MDC1A））引起的早期发作，或者温和的，由于部分层粘连蛋白亚基α2缺乏，儿童或成人发作。对于这两种肌肉疾病，没有治愈性治疗选择，然而，有希望的临床前研究正在进行中。目前,自然史数据缺乏,需要适当的临床和功能结局指标才能达到试验准备状态.
方法：LASTSTRONG是一项针对所有年龄的荷兰语患者的自然史研究，这些患者被诊断为SELENON-RM或LAMA2-MD，从2020年8月开始。在1.5年的时间里，患者在我们医院有四次就诊。在所有访问中,他们接受标准化的神经检查，手持测力（年龄≥5岁），功能测量，问卷(患者报告和/或父母代理人；年龄≥2岁)，肌肉超声包括隔膜，肺功能测试(肺活量测定，最大吸气和呼气压力,嗅鼻吸气压力；年龄≥5岁)，和加速度测量8天(年龄≥2岁)；在第一和三次就诊时，他们接受心脏评估(心电图，超声心动图；年龄≥2岁），脊柱X线（年龄≥2岁），双能X线骨密度仪（DEXA-）扫描（年龄≥2岁）和全身磁共振成像（MRI）（年龄≥10岁）。所有检查都适应患者的年龄和功能能力。将评估后续访问中和之间的关键参数之间的相关性。
结论：我们的研究将描述诊断为SELENON-RM或LAMA2-MD的患者的自然史，使我们能够选择相关的临床和功能结局指标，以达到临床试验准备状态。此外，我们对临床特征的详细描述(深度表型分析)将优化临床管理,并将为前瞻性随访建立一个特征明确的基线队列.
结论：我们的自然史研究是在SELENON-RM和LAMA2-MD中达到试验准备的重要步骤。
背景：本研究已获得医学伦理审查委员会Arnhem-Nijmegen地区（NL64269.091.17，2017-3911）的批准，并在ClinicalTrial.gov（NCT04478981）注册。
方法：LASTSTRONG是一项针对所有年龄的荷兰语患者的自然史研究，这些患者被诊断为SELENON-RM或LAMA2-MD，从2020年8月开始。在1.5年的时间里，患者在我们医院有四次就诊。在所有访问中,他们接受标准化的神经检查，手持测力（年龄≥5岁），功能测量，问卷(患者报告和/或父母代理人；年龄≥2岁)，肌肉超声包括隔膜，肺功能测试(肺活量测定，最大吸气和呼气压力,嗅鼻吸气压力；年龄≥5岁)，和加速度测量8天(年龄≥2岁)；在第一和三次就诊时，他们接受心脏评估(心电图，超声心动图；年龄≥2岁），脊柱X线（年龄≥2岁），双能X线骨密度仪（DEXA-）扫描（年龄≥2岁）和全身磁共振成像（MRI）（年龄≥10岁）。所有检查都适应患者的年龄和功能能力。将评估后续访问中和之间的关键参数之间的相关性。
结论：我们的研究将描述诊断为SELENON-RM或LAMA2-MD的患者的自然史，使我们能够选择相关的临床和功能结局指标，以达到临床试验准备状态。此外，我们对临床特征的详细描述(深度表型分析)将优化临床管理,并将为前瞻性随访建立一个特征明确的基线队列.
结论：我们的自然史研究是在SELENON-RM和LAMA2-MD中达到试验准备的重要步骤。
背景：本研究已获得医学伦理审查委员会Arnhem-Nijmegen地区（NL64269.091.17，2017-3911）的批准，并在ClinicalTrial.gov（NCT04478981）注册。
