Goddard Melissa A, Burlingame Emily, Beggs Alan H, Buj-Bello Anna, Childers Martin K, Marsh Anthony P, Kelly Valerie E
Department of Physiology and Pharmacology, School of Medicine, Wake Forest University, Winston-Salem, NC 27109, USA.
Department of Health and Exercise Science, Wake Forest University, Winston-Salem, NC 27109, USA.
J Neurol Sci. 2014 Nov 15;346(1-2):221-6. doi: 10.1016/j.jns.2014.08.032. Epub 2014 Aug 29.
X-linked myotubular myopathy (XLMTM) is a fatal pediatric disease where affected boys display profound weakness of the skeletal muscles. Possible therapies are under development but robust outcome measures in animal models are required for effective translation to human patients. We established a naturally-occurring canine model, where XLMTM dogs display clinical symptoms similar to those observed in humans. The aim of this study was to determine potential endpoints for the assessment of future treatments in this model. Video-based gait analysis was selected, as it is a well-established method of assessing limb function in neuromuscular disease and measures have been correlated to the patient's quality of life. XLMTM dogs (N = 3) and their true littermate wild type controls (N = 3) were assessed at 4-5 time points, beginning at 10 weeks and continuing through 17 weeks. Motion capture and an instrumented carpet were used separately to evaluate spatiotemporal and kinematic changes over time. XLMTM dogs walk more slowly and with shorter stride lengths than wild type dogs, and these differences became greater over time. However, there was no clear difference in angular measures between affected and unaffected dogs. These data demonstrate that spatiotemporal parameters capture functional changes in gait in an XLMTM canine model and support their utility in future therapeutic trials.
X连锁性肌管性肌病（XLMTM）是一种致命的儿科疾病，患病男孩表现出严重的骨骼肌无力。目前正在研发可能的治疗方法，但要有效地转化应用于人类患者，需要在动物模型中建立可靠的疗效评估指标。我们建立了一种自然发生的犬类模型，患有XLMTM的犬类表现出与人类相似的临床症状。本研究的目的是确定该模型中评估未来治疗方法的潜在终点指标。我们选择了基于视频的步态分析，因为这是评估神经肌肉疾病肢体功能的一种成熟方法，而且相关测量指标与患者的生活质量相关。对3只XLMTM犬及其3只同窝野生型对照犬在4 - 5个时间点进行评估，从10周龄开始，持续到17周龄。分别使用动作捕捉和仪器化地毯来评估随时间变化的时空和运动学变化。与野生型犬相比，XLMTM犬行走速度更慢，步幅更短，而且随着时间推移这些差异变得更大。然而，患病犬和未患病犬在角度测量方面没有明显差异。这些数据表明，时空参数能够捕捉XLMTM犬类模型步态中的功能变化，并支持其在未来治疗试验中的应用。
