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。 这项研究是PTC124在年龄大于或等于18岁的无义突变介导的囊性纤维化(CF)患者中进行的II期、多部位、开放标签、剂量范围、有效性、安全性和PK研究。 Cf是由携带制造Cf跨膜调节蛋白(CFTR)的信息的基因异常引起的。虽然有几个原因可能会导致CFTR蛋白的异常，但有时这种异常会导致CFTR蛋白的缺陷，这被称为CFTR蛋白基因的过早停止(也称为无义突变)。由于这种无义突变，人体细胞(例如，呼吸道、肺或肠道的细胞)中产生的CFTR蛋白不正常，不能正常工作。 这项研究涉及一种名为PTC124的研究药物。这种药物有可能克服无义突变患者的基因缺陷，这种缺陷是囊性纤维化和其他遗传性疾病的基础。对具有无义突变的动物的研究表明，PTC124可能部分恢复了CFTR蛋白的活性。 这项研究的主要目的是了解PTC124是否可以安全地用于人类，以及它是否会增加人体内活性CFTR蛋白的产生。

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. This study is a Phase II, multi-site, open-label, dose-ranging, efficacy, safety, and PK study of PTC124 in subjects aged greater than or equal to 18 years with nonsense-mutation-mediated Cystic Fibrosis (CF). CF is caused by an abnormality in the gene that carries the message for making the CF transmembrane regulator (CFTR) protein. Although there are several reasons why the CFTR protein may be abnormal, sometimes the abnormality leads to a defective CFTR protein which is called a premature stop (also called a nonsense mutation) in the gene for the CFTR protein. Because of this nonsense mutation, the CFTR protein made in the cells of the body (for example, in the cells of the airways, lungs, or bowel) is abnormal and does not work properly. This study involves an investigational drug called PTC124. The drug has the potential to overcome the genetic defect in patients with nonsense mutations as the basis for cystic fibrosis and other genetic disorders. Studies in animals with a nonsense mutation indicate that PTC124 may partially restore the activity of the CFTR protein. The main purpose of this study is to understand whether PTC124 can safely be given to humans and whether it will increase production of active CFTR protein in the person's body.