LEBER CONGENITAL AMAUROSIS DUE TO CEP290 MUTATIONS—SEVERE VISION IMPAIRMENT WITH A HIGH UNMET MEDICAL NEED: A Review. Issue 5 (May 2021)

• Record Type: Journal Article
• Authors: Leroy, Bart P.; Birch, David G.; Duncan, Jacque L.; Lam, Byron L.; Koenekoop, Robert K.; Porto, Fernanda B. O.; Russell, Stephen R.; Girach, Aniz
• Is Part Of: Retina. Volume 41:Issue 5(2021)
• Publication Date: 2021-05
• Subjects: c2991+1655A>G -- CEP290 -- childhood blindness -- ciliopathy -- cone-rod dystrophy -- inherited retinal disease -- LCA10 -- Leber congenital amaurosis; Retina -- Diseases -- Periodicals; Retinal Diseases; Vitreous Body; 617.735
• DOI: 10.1097/IAE.0000000000003133
• Languages: English
• ISSNs: 0275-004X

Abstract

Abstract : Purpose: Leber congenital amaurosis due to CEP290 mutations (LCA10) is an inherited retinal disease that often results in severe visual impairment or blindness in early childhood. Currently, there are no approved treatments, highlighting the considerable unmet medical need associated with LCA10. We aimed to review the clinical characteristics of LCA10, its impact on patients and society, and the investigational treatment strategies currently in development. Methods: Review of the current literature. Results: LCA10 is an autosomal recessive ciliopathy, for which the CEP290 intronic variant c.2991+1655A>G (p.Cys998X) is the most common mutation. Usually diagnosed in early childhood, most patients with LCA10 have severe visual impairment during their first decade of life, which significantly affects the quality of life and development. LCA10 also has a significant societal burden (direct and indirect costs). RNA editing using antisense oligonucleotides or Staphylococcus aureus CRISPR-associated protein-9 nuclease is currently under investigation for treatment of p.Cys998X LCA10. Specifically, the antisense oligonucleotide therapy QR-110 (sepofarsen) has demonstrated encouraging safety and efficacy data in a first-in-human trial; a phase 3 clinical trial is ongoing. Conclusion: Interventions that can preserve or improve vision in patients with LCA10 have considerable potential to improve the patient quality of life and reduce burden of disease. Abstract : Supplemental Digital Content is Available in the Text.In this article, we review the clinical characteristics of Leber congenital amaurosis due to CEP290 mutations (LCA10) and its impact on patients and society. We discuss the challenges associated with differential diagnosis of LCA10, the significant burden of childhood visual impairment, and the investigational treatment strategies currently in development.