体外模型预测罕见基因型患儿 CFTR 调节剂治疗的体内疗效。
Ex vivo model predicted in vivo efficacy of CFTR modulator therapy in a child with rare genotype.
机构信息
Cystic Fibrosis Regional Reference Center,, Department of Paediatric Medicine, Anna Meyer Children's University, Florence, Italy.
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II.
出版信息
Mol Genet Genomic Med. 2021 Apr;9(4):e1656. doi: 10.1002/mgg3.1656. Epub 2021 Mar 13.
BACKGROUND
New drugs that target the basic defect in cystic fibrosis (CF) patients may now be used in a large number of patients carrying responsive mutations. Nevertheless, further research is needed to extend the benefit of these treatments to patients with rare mutations that are still uncharacterized in vitro and that are not included in clinical trials. For this purpose, ex vivo models are necessary to preliminary assessing the effect of CFTR modulators in these cases.
METHOD
We report the clinical effectiveness of lumacaftor/ivacaftor therapy prescribed to a CF child with a rare genetic profile (p.Phe508del/p.Gly970Asp) after testing the drug on nasal epithelial cells. We observed a significant drop of the sweat chloride value, as of the lung clearance index. A longer follow-up period is needed to define the effects of therapy on pancreatic status, although an increase of the fecal elastase values was found.
CONCLUSION
Drug response obtained on nasal epithelial cells correlates with changes in vivo therapeutic endpoints and can be a predictor of clinical efficacy of novel drugs especially in pediatric patients.
背景
针对囊性纤维化（CF）患者基本缺陷的新药现在可能会被用于大量携带可响应突变的患者。然而，仍需要进一步的研究来将这些治疗方法的益处扩展到那些在体外尚未得到充分表征且未纳入临床试验的罕见突变患者。为此，需要体外模型来初步评估这些情况下 CFTR 调节剂的效果。
方法
我们报告了在对一名具有罕见遗传特征（p.Phe508del/p.Gly970Asp）的 CF 儿童进行药物测试后，使用 lumacaftor/ivacaftor 疗法的临床疗效。我们观察到汗液氯化物值显著下降，以及肺部清除指数。需要更长的随访时间来确定治疗对胰腺状况的影响，尽管发现粪便弹性蛋白酶值有所增加。
结论
在鼻上皮细胞上获得的药物反应与体内治疗终点的变化相关，并且可以预测新型药物的临床疗效，特别是在儿科患者中。
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