Validity of a Neurological Scoring System for Canine X-Linked Myotubular Myopathy.
Validity of a Neurological Scoring System for Canine X-Linked Myotubular Myopathy.
复制标题
犬 X 连锁肌管肌病神经评分系统的有效性。
DOI：
10.1089/humc.2015.049
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Childers,MartinK
中科院分区：
文献类型：
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作者：
Snyder,JessicaM;Meisner,Allison;Mack,David;Goddard,Melissa;Coulter,IanT;Grange,Robert;Childers,MartinK
开发了一种简单的临床神经学测试来评估 X 连锁肌管肌病 (XLMTM) 临床前犬模型对基因治疗的反应。这种毁灭性的先天性肌病是由肌管蛋白 (MTM1) 基因突变引起的。临床症状包括肌肉无力、早期呼吸衰竭和呼吸机依赖。与患者相比，自发发生的犬模型具有相似的临床表现和肌肉活检的组织学异常。我们制定了神经肌肉评估评分，评分范围从 10（正常）到 1（无法维持胸骨卧姿）。我们假设这种神经学评估评分与基因型和疾病严重程度的既定衡量标准相关，并且由独立观察者执行时是可靠的。 17 周龄时，神经系统评估分数与既定的严重程度测试方法之间存在很强的相关性。基于独立观察者分配的神经系统评分之间的高度一致性，神经系统严重程度评分正确区分了 XLMTM 和野生型狗，具有良好的观察者间可靠性。总之，这些数据表明针对这种犬先天性神经肌肉疾病开发的神经评分系统是可靠且有效的。该评分系统可能有助于评估该疾病模型的临床前测试中对治疗的反应，例如对基因治疗的反应。
A simple clinical neurological test was developed to evaluate response to gene therapy in a preclinical canine model of X-linked myotubular myopathy (XLMTM). This devastating congenital myopathy is caused by mutation in the myotubularin (MTM1) gene. Clinical signs include muscle weakness, early respiratory failure, and ventilator dependence. A spontaneously occurring canine model has a similar clinical picture and histological abnormalities on muscle biopsy compared with patients. We developed a neuromuscular assessment score, graded on a scale from 10 (normal) to 1 (unable to maintain sternal recumbency). We hypothesize that this neurological assessment score correlates with genotype and established measures of disease severity and is reliable when performed by an independent observer. At 17 weeks of age, there was strong correlation between neurological assessment scores and established methods of severity testing. The neurological severity score correctly differentiated between XLMTM and wild-type dogs with good interobserver reliability, on the basis of strong agreement between neurological scores assigned by independent observers. Together, these data indicate that the neurological scoring system developed for this canine congenital neuromuscular disorder is reliable and valid. This scoring system may be helpful in evaluating response to therapy in preclinical testing in this disease model, such as response to gene therapy.