PDF(Pubmed)
Abstract：
Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with no licensed therapies. Previous Genome Wide Association Studies (GWAS) have identified genes that correlate significantly with PSC, and these were identified by systematic review. Here we use novel Network Proximity Analysis (NPA) methods to identify already licensed candidate drugs that may have an effect on the genetically coded aspects of PSC pathophysiology.Over 2000 agents were identified as significantly linked to genes implicated in PSC by this method. The most significant results include previously researched agents such as metronidazole, as well as biological agents such as basiliximab, abatacept and belatacept. This in silico analysis could potentially serve as a basis for developing novel clinical trials in this rare disease.
摘要：
原发性硬化性胆管炎（PSC）是一种进行性胆汁淤积性肝病，没有许可的治疗方法。先前的全基因组关联研究（GWAS）已经确定了与PSC显着相关的基因，这些是通过系统审查确定的。在这里，我们使用新的网络邻近分析（NPA）方法来鉴定已经获得许可的候选药物，这些药物可能对PSC病理生理学的遗传编码方面产生影响。通过该方法鉴定了超过2000种试剂与PSC中涉及的基因显著相关。最重要的结果包括以前研究过的药物，如甲硝唑，以及生物制剂如巴利昔单抗，abatacept和belatacept.这种计算机模拟分析可能作为开发这种罕见疾病的新型临床试验的基础。
