PTC124 AS AN ORAL TREATMENT FOR NONSENSE-MUTATION-MEDIATED CYSTIC FIBROSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 PTC124是一种新型的口服生物利用的小分子化合物，可促进含有提前终止密码子的信使核糖核酸(MRNA)的核糖体阅读(也称为无义突变)。该药物有可能克服无义突变患者的基因缺陷，作为囊性纤维化(CF)和其他遗传性疾病的基础。PTC124的开发为治疗CF提供了一种独特的策略，将对特定类型的遗传缺陷的检测与一种小分子药物相结合，该药物有可能通过恢复缺失蛋白质的生产来安全地纠正该遗传缺陷的表型表达。 该方案描述了一项2a期、多部位、开放标签、剂量范围、有效性、安全性和药代动力学(PK)的研究，研究对象为18岁至24岁的CF患者。这项研究将作为总体开发计划的一部分进行，旨在获得监管部门的批准，将PTC124用于治疗囊性纤维化跨膜传导调节器(CFTR)基因无义突变引起的CF患者。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PTC124 is a novel, orally bioavailable, small-molecule compound that promotes ribosomal readthrough of messenger ribonucleic acid (mRNA) containing a premature stop codon (also referred to as a nonsense mutation). The drug has the potential to overcome the genetic defect in patients with nonsense mutations as the basis for cystic fibrosis (CF) and other genetic disorders. Development of PTC124 offers a unique strategy for the treatment of CF, coupling testing for a specific type of genetic defect with a small-molecule remedy that has the potential to safely correct the phenotypic expression of that genetic defect by restoring the production of the missing protein. This protocol describes a Phase 2a, multi-site, open label, dose-ranging, efficacy, safety, and pharmacokinetic (PK) study in 18 to 24 CF patients 18 years of age. This study will be conducted as part of an overall development program aimed at obtaining regulatory approval of PTC124 as treatment for patients with CF resulting from a nonsense mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.