Pediatric Gastroenterology Unit, Cystic Fibrosis Center, Hadassah University Hospital, Hebrew University, Jerusalem, 91240 Israel.
Expert Opin Investig Drugs. 2011 Sep;20(9):1285-92. doi: 10.1517/13543784.2011.600304. Epub 2011 Jul 11.
Cystic fibrosis (CF) is the most common lethal monogenic disorder. Life expectancy is rising towards a mean of 40 years, with advances in all aspects of therapy apart from treating the basic defect. Since the discovery of the gene that causes CF, our knowledge of how mutations in this gene cause the varied pathophysiological manifestations of this disease has increased substantially.
This paper discusses the complexities of treatment in CF and the development of therapeutic approaches aimed at the different classes of basic mutation. Apart from gene therapy, several novel compounds have recently been discovered using high-throughput screening, which appear promising enough to develop effective drugs to cure the basic defect. This paper summarizes our current knowledge of gene and mutation-specific therapy and focuses on orally bioavailable potentiators and correctors, particularly suppressors of premature termination codons, including preclinical model systems and clinical trials in CF.
The further development of these drugs will enable treatment of the basic defect in diseases such as CF, and open the door for treatment of disease according to gene sequencing: true personalized medicine.
囊性纤维化（CF）是最常见的致命性单基因疾病。除了治疗基本缺陷外，随着治疗各方面的进步，预期寿命正在向平均 40 年延长。自发现导致 CF 的基因以来，我们对该基因中的突变如何导致这种疾病的各种病理生理表现的了解有了实质性的增加。
本文讨论了 CF 治疗的复杂性以及针对不同基本突变类型的治疗方法的发展。除了基因治疗外，最近还使用高通量筛选发现了几种新型化合物，它们似乎很有前途，可以开发出有效的药物来治愈基本缺陷。本文总结了我们目前对基因和突变特异性治疗的了解，并重点介绍了口服生物利用度的增效剂和校正剂，特别是终止密码子通读抑制物，包括 CF 的临床前模型系统和临床试验。
这些药物的进一步发展将使 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开辟道路：真正的个性化医疗。
