Wilschanski Michael
Pediatric Gastroenterology Unit, Division of Pediatrics, Hadassah Hospitals, Hebrew University, Jerusalem 91240, Israel.
Discov Med. 2013 Feb;15(81):127-33.
Cystic fibrosis (CF) is the most common lethal monogenic disorder. Life expectancy of CF patients is rising towards a mean of 40 years with advances in all aspects of therapy apart from treating the basic molecular defect. In the twenty three years since the discovery of the gene that causes cystic fibrosis, our knowledge of how mutations in this gene cause the varied pathophysiological manifestations of this disease has increased substantially. This knowledge has led to the possibility of new therapeutic approaches aimed at the basic defect. Apart from gene therapy, several novel compounds have recently been discovered using high-throughput screening which appear promising enough to develop into effective drugs to cure the basic defect. This article will summarize our current knowledge of mutation specific therapy and will focus on orally bioavailable potentiators and correctors and suppressors of premature termination codons. Further development of these drugs will enable treatment of the basic defect in diseases like CF and open the door for treatment of disease according to gene sequencing -- true personalized medicine.
囊性纤维化（CF）是最常见的致死性单基因疾病。随着除治疗基本分子缺陷外的各方面治疗取得进展，CF患者的预期寿命正朝着平均40岁攀升。自发现导致囊性纤维化的基因以来的二十三年里，我们对该基因突变如何引发这种疾病多样的病理生理表现的认识有了大幅增加。这些认识催生了针对基本缺陷的新治疗方法的可能性。除了基因治疗，最近通过高通量筛选发现了几种新型化合物，它们看起来有足够的潜力发展成为治愈基本缺陷的有效药物。本文将总结我们目前对突变特异性治疗的认识，并将重点关注口服生物可利用的增效剂、校正剂和提前终止密码子抑制剂。这些药物的进一步研发将使CF等疾病的基本缺陷得到治疗，并为根据基因测序进行疾病治疗——真正的个性化医疗打开大门。
