伏索里提德治疗对IGF-I和C型内源性性尿性的作用 在低染色体增生症中
Roopa Kanakatti Shankar1,2, Despoina M Galetaki1, Anqing Zhang3
1Division of Endocrinology, Children's National Hospital, Washington, DC, USA.
在患有性质过高症 (HCH) 的儿童中,胰岛素样生长因子-1 (IGF-1) 水平较低,C型尿素 (CNP) 水平较高. 沃索里提德治疗显示IGF-1和NTproCNP的变化之间存在相关性,这表明存在潜在的相互作用.
科学领域:
- 儿科内分泌学 儿科内分泌学
- 骨发育不良症 骨发育不良症
- 增长因子信号表示
背景情况:
- 胰岛素样生长因子-1 (IGF-1) 和C型尿素 (CNP) 是内分泌骨生长的关键调节剂.
- 伏索里提德 (vosoritide) 是一种CNP类似物,此前已经证明其有效性,改善了患有下极性质形成症 (HCH) 的儿童的生长.
研究的目的:
- 为了研究IGF-1和CNP在患有HCH的儿童之间的基线关系.
- 为了研究IGF-1和NTproCNP在vosoritide治疗期间的纵向变化和相关性.
- 评估这些生长因素与身高和生长速度的变化之间的关联.
主要方法:
- 一个为期12个月的,单臂,非盲目的Vosoritide (15μg/kg/day) 的II期临床试验,用于患有HCH的青春期前儿童 (3-11岁).
- 在基线和每6个月测量人类学,IGF-1和NTproCNP.
- 增长参数的纵向分析和增长因素与增长结果之间的相关性分析.
主要成果:
- 患有HCH的儿童表现出基线IGF-1水平降低和基线NTproCNP水平升高.
- 虽然IGF-1水平在治疗期间增加,但IGF-1标准偏差 (SD) 没有显著变化.
- 在治疗期间,NTproCNP水平下降,在6个月和12个月观察到明显较低的NTproCNP SD;身高SD或年增长速度 (AGV) 的变化与IGF-1或NTproCNP SD无关.
- 在12个月的IGF-1和NTproCNP度变化之间发现了正相关性 (Rho=0.57,p=0.024).
结论:
- 在患有HCH的儿童中,基线IGF-1降低,NTproCNP升高.
- 沃索里提德治疗导致IGF-1和NTproCNP水平发生变化.
- 在IGF-1和NTproCNP的变化之间观察到的相关性表明,这些信号通路在Vosoritide治疗期间在HCH之间存在潜在的相互作用.
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