Personalized Cystic Fibrosis Therapy and Research Center

摘要/摘要 囊性纤维化是由于囊性纤维化跨膜电导缺失或功能障碍引起的 调节剂 (CFTR) 氯离子通道。 CFTR 缺陷与基因变异密切相关 CFTR 基因对于个体 CF 患者或 CF 患者群体中的亚组是独特的。因此，一个 个性化医疗方法有助于根据独特的分子特征为个体 CF 患者定制护理 以及与其 CFTR 基因相关的表型特征。这将推动成功的治疗 结果并最大限度地减少长期治疗的潜在副作用。鉴于我们位于 CCHMC 的 CF 中心 已经拥有优秀的电子病历系统 (EPIC) 和特定地点 IRB 批准的基因型 可供临床和研究使用的数据库，我们打算利用这些功能来开发 个性化囊性纤维化治疗和研究中心 (PCFC) 为个体患者 (i) 确定 他/她对特定形式的 CF 突变的易感性，并且 ii) 采取措施减轻早期发作 疾病。最后，CF 研究的未来为各种 CFTR 靶向疗法提供了潜力（即， CFTR 调节剂）来治疗 CF 的根本原因，目前有多种调节剂处于不同阶段 发展。

SUMMARY/ABSTRACT Cystic Fibrosis results from the absence or dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel. Defects in CFTR are strongly associated with genetic variations in the CFTR gene that are unique to individual CF patients or to subgroups within the CF patient population. Thus, a personalized medicine approach helps customize care to individual CF patients based on the unique molecular and phenotypic characteristics associated with their CFTR gene. This will drive successful therapeutic outcomes and minimize potential adverse effects of chronic therapies. Given that our CF Center at CCHMC already has an excellent electronic medical record system (EPIC) and a site-specific IRB approved genotype database available for clinical and research use, we intend to leverage these capabilities to develop Personalized Cystic Fibrosis Therapy and Research Center (PCFC) for individual patients to (i) determine his/her susceptibility to a particular form of CF mutation, and ii) take steps to mitigate the early onset of the disease. Finally, the future of CF research offers the potential for a variety of CFTR-targeted therapies (i e., CFTR modulators) to treat the underlying cause of CF, with multiple modulators currently in different stages of development.