BackgroundFragile X is the most common form of inherited intellectual disability and the leading known genetic cause of autism. There is currently no cure or approved medication for fragile X although various drugs target specific disease symptoms and a large number of therapeutics are in various stages of clinical development. Multiple recent clinical trials have failed on their primary endpoints indicating that there is a compelling need for validated biomarkers and outcome measures in fragile X.FindingsThere are currently no validated blood-based biomarkers to assess disease severity or to monitor drug efficacy in fragile X syndrome. Herein, we review candidate blood protein biomarkers including extracellular-regulated kinase, phosphoinositide 3-kinase, matrix metalloproteinase 9, amyloid-beta and amyloid-beta protein precursor.ConclusionsBench-to-bedside plans for fragile X syndrome are severely limited by the lack of validated outcome measures. The reviewed candidate biomarkers are at early stages of validation and deserve further investigation.

中文翻译：

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寻找脆弱的 X 生物标志物

背景脆性 X 是遗传性智力障碍的最常见形式，也是导致自闭症的主要已知遗传原因。尽管各种药物针对特定的疾病症状，并且大量疗法处于临床开发的不同阶段，但目前尚无治愈或批准的药物治疗脆性 X。最近多项临床试验的主要终点均失败，表明迫切需要验证脆弱 X 的生物标志物和结果指标。发现目前没有经过验证的基于血液的生物标志物来评估疾病严重程度或监测脆性 X 综合征的药物疗效。在此，我们回顾了候选血液蛋白质生物标志物，包括细胞外调节激酶、磷酸肌醇 3-激酶、基质金属蛋白酶 9、淀粉样蛋白-β 和淀粉样蛋白-β 蛋白前体。结论 由于缺乏经过验证的结果措施，针对脆性 X 综合征的从实验室到床边的计划受到严重限制。审查的候选生物标志物处于验证的早期阶段，值得进一步研究。