Revisión sobre terapia génica aprobada y recuperación visual en la amaurosis congénita de Leber por mutación en el gen RPE65

Marcela Ciccioli; Alejandra Antacle

doi:10.70313/2718.7446.v17.n01.284

Autores

Marcela Ciccioli Asociación de Padres de Niños con Enfermedad de Stargardt (Stargardt APNES) y Retina Argentina, Buenos Aires, Argentina. PANIRD Professors (Panamerican Inherited Retinal Diseases Group).
Alejandra Antacle Pontificia Universidad Católica Argentina, Buenos Aires, Argentina. Universidad del Salvador, Buenos Aires, Argentina

DOI:

https://doi.org/10.70313/2718.7446.v17.n01.284

Palavras-chave:

Amaurose congênita de Leber, distrofias hereditárias da retina, gene RPE65, terapia gênica

Resumo

As distrofias hereditárias da retina são um grupo de condições visuais que levam progressivamente à baixa visão e/ou à cegueira. Atualmente, sabe-se que mais de 390 genes diferentes estão envolvidos na causa dessas distrofias. A amaurose congênita de Leber apresenta-se congenitamente ou antes do primeiro ano de vida e é uma das distrofias retinianas mais graves de início precoce. A amaurose congênita de Leber e/ou retinose pigmentar tipo 20 devido a variantes bi-alélicas patogênicas no gene RPE65 é, até o momento, a única distrofia que tem tratamento genético aprovado por diferentes agências reguladoras internacionais, incluindo a Argentina desde 2021 (autorizado pela ANMAT). Atualmente, estão sendo desenvolvidos protocolos para novas terapias gênicas para outras anomalias, como a doença de Stargardt, a síndrome de Usher tipo IB, a retinite pigmentosa devido a mutações no gene RPGR, a coroideremia e muitas outras. Este artigo fará uma revisão dos conceitos atuais dessa doença e de sua terapia gênica.

Downloads

Os dados de download ainda não estão disponíveis.

Referências

Cremers FPM, Boon CJF, Bujakowska K, Zeitz C. Special issue introduction: Inherited retinal disease: novel candidate genes, genotype-phenotype correlations, and inheritance models. Genes (Basel) 2018; 9: 215.

Motta FL, Martin RP, Filippelli-Silva R et al. Relative frequency of inherited retinal dystrophies in Brazil. Sci Rep 2018; 8: 15939.

Viriato D, Bennett N, Sidhu R et al. An economic evaluation of voretigene neparvovec for the treatment of biallelic RPE65- mediated inherited retinal dystrophies in the UK. Adv Ther 2020; 37: 1233-1247.

O’Neal TB, Luther EE. Retinitis pigmentosa. En: StatPearls [en línea]. Treasure Island (FL): StatPearls, 2023. Disponible en: https://www.ncbi.nlm. nih.gov/books/NBK519518/

Aouadj C, Banhazi J, Shaikh J et al. Epidemiology of RPE65 gene mutation related inherited retinal dystrophies: a systematic literature review [abstract no. PSY28]. Value Health 2018; 21 (Suppl 3): S440.

Astuti GDN, Bertelsen M, Preising MN et al. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark. Eur J Hum Genet 2016; 24: 1071-1079.

Darrow JJ. Luxturna: FDA documents reveal the value of a costly gene therapy. Drug Discov Today 2019; 24: 949-954.

Thompson DA, Ali RR, Monaciano Consortium et al. Advancing therapeutic strategies for inherited retinal degeneration: recommendations from the Monaciano Symposium. Invest Ophthalmol Vis Sci 2015; 56: 918-931.

Travis GH, Golczak M, Moise AR, Palczewski K. Diseases caused by defects in the visual cycle: retinoids as potential therapeutic agents. Annu Rev Pharmacol Toxicol 2007; 47: 469-512.

Jacobson SG, Aleman TS, Cideciyan AV et al. Identifying photoreceptors in blind eyes caused by RPE65 mutations: prerequisite for human gene therapy success. Proc Natl Acad Sci USA 2005; 102: 6177-6182.

Kumaran N, Pennesi ME, Yang P et al. Leber congenital amaurosis / Early-onset severe retinal dystrophy overview. En: Adam MP, Ardinger HH, Pagon RA et al. (eds). GeneReviews [en línea]. Seattle: University of Washington at Seattle, 2023. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK531510/.

Cideciyan AV. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res 2010; 29: 398-427.

Cideciyan AV, Jacobson SG, Beltran WA et al. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci USA 2013; 110: E517-E525.

Sen M, Honavar SG. Theodor Karl Gustav von Leber: the sultan of Selten. Indian J Ophthalmol 2022; 70: 2218-2220.

Waardenburg PJ, Schappert-Kimmijser J. On various recessive biotypes of Leber’s congenital amaurosis. Acta Ophthalmol (Copenh) 1963; 41: 317-320.

Huang D, Swanson EA, Lin CP et al. Optical coherence tomography. Science 1991; 254: 1178-1181.

Chung DC, McCague S, Yu ZF et al. Novel mobility test to assess functional vision in patients with inherited retinal dystrophies. Clin Exp Ophthalmol 2018; 46: 247-259.

Chung DC, Lee K, Reape KZ et al. Long-term efect of voretigene neparvovec on the full-feld light densitivity threshold test of patients with RPE65 mutation-associated inherited retinal dystrophy: post hoc analysis of phase I trial data [abstract]. Investig Ophthalmol Vis Sci 2019; 60: 3398.

Chung DC, Bertelsen M, Lorenz B et al. The natural history of inherited retinal dystrophy due to biallelic mutations in the RPE65 gene. Am J Ophthalmol 2019; 199: 58-70.

Bennett J, Wellman J, Marshall KA et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet 2016; 388: 661-672.

Leroy BP, Drack A, Bennett J et al. Duration of effect of ocular gene therapy: 4 year follow-up data from the phase III voretigene neparvovec trial in patients with biallelic RPE65 mutation associated retinal dystrophy [abstract]. En: Euretina Congress (19th: 2019: Paris). Programme.

Maguire AM, High KA, Auricchio A et al. Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis: a phase 1 dose-escalation trial. Lancet 2009; 374: 1597-1605.

Russell SR, Maguire AM, Bennett J et al. Visual function questionnaire responses in the voretigene neparvovec phase 3 trial [abstract]. Investig Ophthalmol Vis Sci 2019; 60: 4968.

Drack AV, Bennett J, Russell S et al. How long does gene therapy last? 4-year follow-up of phase 3 voretigene neparvovec trial in RPE65-associated LCA/inherited retinal disease [abstract no. 017]. J AAPOS 2019; 23: e7.

Russell SR, Bennett J, Wellman JA et al. Year 2 results for a phase 3 trial of voretigene neparvovec in biallelic RPE65-mediated inherited retinal disease [abstract]. Investig Ophthalmol Vis Sci 2017; 58: 4122.

Russell SR, Bennett J, Wellman J et al. Three-year update for the phase 3 voretigene neparvovec study in biallelic RPE65 mutationassociated inherited retinal disease [abstract]. Investig Ophthalmol Vis Sci 2018; 59: 3900.

Ziccardi L, Cordeddu V, Gaddini L et al. Gene therapy in retinal dystrophies. Int J Mol Sci 2019; 20: 5722.

Hanein S, Perrault I, Gerber S et al. Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis. Hum Mutat 2004; 23: 306-317.

Kumaran N, Ripamonti C, Kalitzeos A et al. Severe loss of tritan color discrimination in RPE65 associated Leber congenital amaurosis. Invest Ophthalmol Vis Sci 2018; 59: 85-93.

Zimmermann M, Lubinga SJ, Banken R et al. Cost utility of voretigene neparvovec for biallelic RPE65-mediated inherited retinal disease. Value Health 2019; 22: 161-167.

Richards S, Aziz N, ACMG Laboratory Quality Assurance Committee et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17: 405-424.

European Medicines Agency. [Luxturna]: summary of product characteristics Amsterdam, 2019. Disponible en: https://www.ema.europa.eu/en/documents/product-information/luxturna-epar-product-information_en.pdf

Russell SR, Maguire AM, Bennett J et al. Visual function questionnaire responses in the voretigene neparvovec phase 3 trial [abstract]. Investig Ophthalmol Vis Sci 2019; 60: 4968.

Spark Therapeutics. Luxturna [US prescribing information]. Disponible en: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/luxturna

Fischer MD, Simonelli F, PERCEIVE Study Group et al. Real-world safety and effectiveness of voretigene neparvovec: results up to 2 years from the prospective, registry-based PERCEIVE study. Biomolecules 2024; 14: 122.

Lorenz B, Wabbels B, Wegscheider E et al. Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65. Ophthalmology 2004; 111: 1585-1594.

Johnson S, Buessing M, O’Connell T et al. Cost-effectiveness of voretigene neparvovec-rzyl vs standard care for RPE65-mediated inherited retinal disease. JAMA Ophthalmol 2019; 37: 1115-1123.