新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » BIOON报道 » NEJM:阿巴西普有望成为肾脏疾病的首个靶向治疗药物

NEJM:阿巴西普有望成为肾脏疾病的首个靶向治疗药物

来源:生物谷 2013-11-11 22:21

2013年11月11日讯 /生物谷BIOON/--近日,马萨诸塞州总医院(MGH)研究人员报告称,已被批准用于治疗类风湿关节炎的药物--Abatacept(阿巴西普)也可能成为第一个靶向治疗节段性肾小球硬化(FSGS)的药物,FSGS几乎不可避免地会导致肾功能衰竭。研究报告发表在New England Journal of Medicine杂志上。

麻省总医院医学系肾脏病科、新英格兰医学杂志资深作者Peter Mundel医学博士说:我们确定阿巴西普或可作为第一个个性化、针对性的药物治疗FSGS。

研究还确定了可以帮助辨别哪些患者最有可能受益于阿巴西普治疗的生物标志物。FSGS的疾病特征在于肾小球中形成瘢痕组织,肾小球是肾脏必不可少的过滤单元。FSGS的发病某些是由遗传原因引发的,然而还有一些​致病原因是未知的,但绝大多数情况下,高血压,肥胖或糖尿病个人易患FSGS。

虽然致病机制目前尚不清楚,但FSGS会扰乱足细胞(肾小球内的细胞)的功能,足细胞对肾功能是至关重要的。虽然类固醇激素和一些免疫抑制药物治疗可以帮助一些病人,但药物长期使用容易导致副作用。Mundel研究小组先前的研究发现,表达于足细胞的免疫分子B7-1在肾脏过滤功能破坏中发挥重要作用,肾脏过滤功能破坏导致蛋白渗漏进入尿液中(蛋白尿),最终导致肾功能衰竭。

目前批准用于类风湿关节炎治疗的药物阿巴西普能抑制B7-1的活性,B7-1在健康的足细胞中不表达。经过体外试验表明,阿巴西普能阻断足细胞B7-1的表达,五位FSGS患者给予药物后,其中四位为疾病复发性患者,一位为抵抗治疗(肾功能衰竭高风险)的疾病患者。

在所有5例患者中,阿巴西普治疗能缓解FSGS造成的蛋白尿。四位疾病复发性患者在接受阿巴西普单剂量治疗后,两位患者的疾病症状缓解期长达三年和四年。五位患者中的两位患者当蛋白尿再次出现时需要再服用阿巴西普,他们的疾病缓解期分别为10个月和12个月,而肾功能衰竭高风险FSGS患者已经恢复了正常的生活。

虽然肾功能衰竭高风险的FSGS患者每月不断服用阿巴西普,但她不再需要高剂量的类固醇和免疫抑制药物,其中一些类固醇和免疫抑制药物实际上反而可能增加肾功能衰竭的风险。哈佛医学院医学副教授Mundel解释说,大规模的临床试验是必要的,他和他的同事们都希望阿巴西普将被证明能有效治疗肾脏疾病。(生物谷Bioon.com)

A New Era of Podocyte-Targeted Therapy for Proteinuric Kidney Disease

Brje Haraldsson, M.D., Ph.D.

Stage 5 chronic kidney disease, which heralds end-stage renal disease (ESRD) and the need for dialysis or transplantation, is a major and rapidly increasing socioeconomic burden worldwide. In 2011, approximately 113,000 patients began dialysis therapy in the United States.1 At the end of 2011, approximately 430,000 Americans were on dialysis and another 186,000 had functioning kidney transplants, which brought the total number of patients with ESRD in the United States to 616,000.1

Glomerular disease is the most common cause of ESRD, accounting for almost two thirds of cases. In recent years, a complex and fascinating world of molecular mechanisms that contribute to the glomerular filtration barrier has been unveiled.2 Each human kidney contains, on average, about a million glomeruli, through which an ultrafiltrate of the blood passes, normally producing about 180 liters of filtrate per day, most of which is reabsorbed in the kidney tubules. The filtering apparatus is intricate — it consists of glomerular capillary endothelial cells, the glomerular basement membrane, and then podocytes, which comprise the final barrier. The functional properties of this elaborate structure are not fully understood, but we know that larger solutes, such as albumin, are retarded in their transglomerular passage depending on size, charge, and molecular shape.3 The primary urine (plasma ultrafiltrate) in Bowman's space has a concentration of albumin that is less than 10?4 times the plasma concentration of albumin; smaller solutes pass largely unimpeded.3 However, the glomerular filtration mechanism goes awry in glomerulopathies, at times leaking large amounts of protein into the urine.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库