临床试验的蛋白质Farnesylation抑制剂Lonafarnib,普伐他汀,Zoledronic酸Hutchinson-Gilford儿童早衰症综合征。

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戈登磅,Kleinman我,马萨罗J, RB达Sr, Shappell H, Gerhard-Herman M,斯穆特磅,戈登厘米,克利夫兰RH, Nazarian,斯奈德BD,乌尔里希新泽西,Silvera VM,梁MG,奎因N,米勒DT,嗯SY, Dowton AA, Littlefield K,格里尔毫米,基兰兆瓦

临床试验的蛋白质Farnesylation抑制剂Lonafarnib,普伐他汀,Zoledronic酸Hutchinson-Gilford儿童早衰症综合征。

循环。2016年7月12日,134(2):114 - 25所示。doi: 10.1161 / CIRCULATIONAHA.116.022188。

PubMed ID

27400896 (在PubMed

]

文摘

背景:Hutchinson-Gilford早衰症综合征是一种极其罕见的,致命的,节段性早衰突变引起的综合症LMNA产生farnesylated progerin异常的蛋白质。没有progerin-specific治疗,死亡就发生在平均年龄14.6岁的加速动脉粥样硬化。前一个单臂临床试验表明,蛋白质治疗抑制剂lonafarnib改善心血管和骨骼疾病的某些方面。现在审判为了进一步提高疾病,此外抑制progerin prenylation。方法:37参与者Hutchinson-Gilford早衰症综合征收到普伐他汀,zoledronic酸,lonafarnib。这种联合治疗评估,除了描述性比较前lonafarnib单一疗法试验。结果:没有参与者退出,因为副作用。主要结果成功被改进的预定义的平均体重增加或颈动脉echodensity率;71.0%的参与者成功(P < 0.0001)。主要心血管和骨骼辅助变量被预定义。 Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial. CONCLUSIONS: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.

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药物

Lonafarnib