The Value of Imaging and Composition-Based Biomarkers in Duchenne Muscular Dystrophy Clinical Trials
The Value of Imaging and Composition-Based Biomarkers in Duchenne Muscular Dystrophy Clinical Trials
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DOI：
10.1007/s13311-019-00825-1
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发表时间：
2019-12-26
影响因子：
5.7
通讯作者：
Rutkove, Seward B.
中科院分区：
文献类型：
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作者：
Chrzanowski, Stephen M.;Darras, Basil T.;Rutkove, Seward B.
随着治疗Duchenne肌营养不良症(DMD)的药物开发流水线的快速推进，临床试验结果需要优化。在杜氏肌营养不良的临床试验中，对疾病负担、自然病程进展和治疗反应的有效评估是临床试验成功的关键因素。通过选择最佳的生物标记物来更好地评估治疗效果，可以降低研究成本和样本量要求。目前，功能性测量仍然是大多数DMD临床试验的主要结果。肌肉健康的定量测量，包括磁共振成像和光谱、电阻抗肌图和超声波，可以灵敏地识别病变肌肉、疾病进展和对治疗干预的反应。此外，这种非侵入性技术有可能在临床症状出现之前识别疾病病理。尽管有强有力的证据支持，非侵入性定量技术仍然不经常用于杜氏肌营养不良的临床试验。非侵入性定量技术已经证明了量化疾病进展和对治疗干预的潜在反应的能力，应该作为当前标准功能测量的补充。这些方法有可能极大地加快DMD疗法的开发和批准。
As the drug development pipeline for Duchenne muscular dystrophy (DMD) rapidly advances, clinical trial outcomes need to be optimized. Effective assessment of disease burden, natural history progression, and response to therapy in clinical trials for Duchenne muscular dystrophy are critical factors for clinical trial success. By choosing optimal biomarkers to better assess therapeutic efficacy, study costs and sample size requirements can be reduced. Currently, functional measures continue to serve as the primary outcome for the majority of DMD clinical trials. Quantitative measures of muscle health, including magnetic resonance imaging and spectroscopy, electrical impedance myography, and ultrasound, sensitively identify diseased muscle, disease progression, and response to a therapeutic intervention. Furthermore, such non-invasive techniques have the potential to identify disease pathology prior to onset of clinical symptoms. Despite robust supportive evidence, non-invasive quantitative techniques are still not frequently utilized in clinical trials for Duchenne muscular dystrophy. Non-invasive quantitative techniques have demonstrated the ability to quantify disease progression and potential response to therapeutic intervention, and should be used as a supplement to current standard functional measures. Such methods have the potential to significantly accelerate the development and approval of therapies for DMD.