Case Study: Single Injection of RNA Therapy Improved Vision with Lasting Effect in LCA Patient

Article: A Single Injection Reverses Blindness in Patient with Rare Genetic Disorder
Source: Penn Medicine News, via ScienceDaily
Published: April 1, 2021
Article: Mutation-Specific RNA Therapy Can Improve Vision with Lasting Effects
Source: Genetic Engineering & Biotechnology News
Published: April 5, 2021

Sustained visual improvement at 15 months
with single injection of sepofarsen

This study presents an unexpected case of sustained visual improvement at 15 months following a single injection of RNA therapy. The case study was part of a 2018 clinical trial involving eleven patients with Leber congenital amaurosis (LCA) due to a mutation in the CEP290 gene, one of the more common variants of the disease. People with this form of LCA suffer from severe visual impairment, typically beginning in infancy, due to abnormal development of the cilia of their photoreceptors. Specifically, the researchers investigated intravitreal injection of the RNA antisense oligonucleotide sepofarsen at three-month intervals for improvement of foveal structure and visual function. Unlike the other ten patients in the clinical trial, the patient in question elected to forgo quarterly maintenance doses after the initial injection due to concerns of cataract development. Surprisingly, however, more than a dozen measurements of visual function and retinal structure showed marked improvement, which peaked between 2 and 3 months and were sustained with mild reduction at 15 months. The researchers suggest that the success of antisense oligonucleotide therapy, which works to increase normal protein levels in the eye's photoreceptors, is due to the fact that these RNA molecules are tiny enough to get into the cell nucleus and have a slow natural rate of degradation, both contributing to their lasting effect. What is interesting about this case is that it inadvertently provides a comparison between two dosing schedules. One of the researchers notes, “The unexpected stability of the ciliary transition zone noted in the patient prompts reconsideration of dosing schedules for sepofarsen, as well as other cilium-targeted therapies.”

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Cideciyan AV, Jacobson SG, Ho AC, et al. "Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report." Nature Medicine.  27:785-789. 1 April 2021. https://doi.org/10.1038/s41591-021-01297-7