Brennan Amanda L, Geddes Duncan M
St. George's Hospital Medical School, Tooting, UK.
Pediatr Pulmonol. 2004 Feb;37(2):87-98. doi: 10.1002/ppul.10407.
The discovery of the cystic fibrosis transmembrane conductance regulator gene in 1989 led to a dramatic increase in the understanding of the molecular basis of CF. Increased knowledge has provided the opportunity to target drug development at correcting the basic defect either by gene therapy or pharmacological modulation of the abnormal physiological processes. Development of new medications for the CF population poses many challenges. The discovery and development of new medications is always time consuming and expensive. Since CF affects a small population worldwide, the potential for a drug company to profit from a new treatment is limited. In addition, each new therapy must have an additional and proven benefit to be attractive to clinicians and consumers, otherwise it will not be commercially viable. Demonstrating clinical benefit is problematic as a limited number of patients are available to participate in clinical trails and outcome measures, such as length of life, are hard to measure. In this review we will illustrate these challenges by discussing the development of treatments which have successfully reached the bedside and those that were unsuccessful.
1989年囊性纤维化跨膜传导调节因子基因的发现，极大地增进了人们对囊性纤维化分子基础的理解。知识的增加为药物研发提供了机会，可通过基因治疗或对异常生理过程进行药理学调节来纠正基本缺陷。为囊性纤维化患者群体开发新药物面临诸多挑战。新药物的发现和开发总是耗时且昂贵的。由于囊性纤维化在全球影响的人群较少，制药公司从新疗法中获利的潜力有限。此外，每种新疗法必须有额外且已证实的益处，才能吸引临床医生和消费者，否则它在商业上就不可行。证明临床益处存在问题，因为可供参与临床试验的患者数量有限，而且诸如寿命长度等结果指标很难衡量。在本综述中，我们将通过讨论已成功应用于临床的治疗方法以及未成功的治疗方法的开发情况，来说明这些挑战。
