Cideciyan Artur V, Jacobson Samuel G, Ho Allen C, Garafalo Alexandra V, Roman Alejandro J, Sumaroka Alexander, Krishnan Arun K, Swider Malgorzata, Schwartz Michael R, Girach Aniz
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Wills Eye Hospital, Thomas Jefferson University, Philadelphia PA, USA.
Nat Med. 2021 May;27(5):785-789. doi: 10.1038/s41591-021-01297-7. Epub 2021 Apr 1.
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.
正在探索使用反义寡核苷酸（AON）司泊法新治疗由CEP290纤毛病引起的莱伯先天性黑蒙。一名参与更大队列研究（ClinicalTrials.gov NCT03140969）的患者在单次玻璃体内注射司泊法新后接受了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近3个月达到了显著的疗效峰值。在15个月时，尽管有证据表明从峰值反应有所下降，但仍有持续疗效。疗效动力学可以通过AON驱动的新CEP290蛋白合成与人类中央凹视锥光感受器中CEP290蛋白缓慢的自然降解率之间的平衡来解释。
