Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report.

用反义寡核苷酸 sepofarsen 单次治疗后可持久改善视力 ： 一例病例报告。

• 影响指数: 87.241
• 发表时间: 05 2021
• 来源期刊: Nat Med
• DOI: 10.1038/s41591-021-01297-7
• PMID: 33795869
• 文章类型: Case Reports
• 中科院分区: Q1
• 方向: 生物
• 作者列表: Cideciyan AV,Jacobson SG,Ho AC,Garafalo AV,Roman AJ,Sumaroka A,Krishnan AK,Swider M,Schwartz MR,Girach A

Mesh: Antigens, Neoplasm / genetics metabolism; Cell Cycle Proteins / genetics metabolism; Ciliopathies / genetics therapy; Cytoskeletal Proteins / genetics metabolism; Genetic Therapy / methods; Humans; Leber Congenital Amaurosis / genetics physiopathology therapy; Oligonucleotides, Antisense / therapeutic use; Photoreceptor Cells / metabolism; Vision, Ocular / physiology; Visual Fields / physiology

Abstract

Leber congenital amaurosis due to CEP290 ciliopathy is being explored by treatment with the antisense oligonucleotide (AON) sepofarsen. One patient who was part of a larger cohort (ClinicalTrials.gov NCT03140969 ) was studied for 15 months after a single intravitreal sepofarsen injection. Concordant measures of visual function and retinal structure reached a substantial efficacy peak near 3 months after injection. At 15 months, there was sustained efficacy, even though there was evidence of reduction from peak response. Efficacy kinetics can be explained by the balance of AON-driven new CEP290 protein synthesis and a slow natural rate of CEP290 protein degradation in human foveal cone photoreceptors.

摘要

正在通过使用反义寡核苷酸（AON）sepofarsen治疗来探索由于CEP290纤毛病引起的Leber先天性黑蒙。一名患者是一个更大的队列（ClinicalTrials.govNCT03140969）的一部分，在单次玻璃体内注射sepofarsen后进行了15个月的研究。视觉功能和视网膜结构的一致测量在注射后3个月左右达到了实质性的疗效峰值。15个月时,有持续的疗效，即使有证据表明从峰值反应减少。功效动力学可以通过AON驱动的新CEP290蛋白合成的平衡和人中央凹锥体光感受器中CEP290蛋白降解的缓慢自然速率来解释。