EYES ON A BRIGHTER FUTURE: EMERGING IRD GENE THERAPIES

Science is advancing

Over 40 clinical trials are either completed or underway for different types of inherited retinal diseases (IRDs), such as RP, XLRP, LCA, ACHM, USH, and Stargardt disease1

Today, there are FDA- and EMA-approved gene therapies on the market, including one for an IRD caused by biallelic variants in the RPE65 gene1,2

Testing for IRDs now includes gene sequencing for more than 270 IRD-related genes. Innovative vision-guided mobility assessments (VMAs) can now more accurately measure functional vision3-8

Gene therapy milestones 1,9-11

Explore the latest clinical trials that are underway and be inspired by advancing science

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Innovative gene therapies are on the horizon

Novel gene therapy trials are underway for a wide range of IRDs, and more are on the horizon. Retinal surgeons may soon have more advanced treatment options to add to their armamentarium. There are several approaches to gene therapies under investigation, such as¹²:

Normal copy of mutated gene inserted into the host cells through gene replacement therapy (augmentation therapy)Normal copy of mutated gene inserted into the host cells through gene replacement therapy (augmentation therapy)

Gene replacement therapy

During gene replacement therapy, also known as augmentation therapy, a retinal surgeon inserts normal copies of the mutated gene into the host cells.¹³

Gene variant corrected within the host DNA through gene editing, a type of gene therapyGene variant corrected within the host DNA through gene editing, a type of gene therapy

Gene editing

Gene editing corrects the gene variant directly within the host DNA.¹⁴

Ribonucleic acid (RNA) being altered through RNA editing, a type of gene therapyRibonucleic acid (RNA) being altered through RNA editing, a type of gene therapy

RNA editing

RNA editing edits the RNA, not the DNA. This enables the editing of pathogenic variants at a transcript level.¹⁴

Meghan, an ophthalmic genetic counselor for patients with inherited retinal diseases (IRDs)

Everything excites me about the idea of gene therapy and the ability to offer a sense of hope to people affected by inherited retinal diseases.

– Meghan, ophthalmic genetic counselor

Meghan, an ophthalmic genetic counselor for patients with inherited retinal diseases (IRDs)

Everything excites me about the idea of gene therapy and the ability to offer a sense of hope to people affected by inherited retinal diseases.

– Meghan, ophthalmic genetic counselor

The eye is an optimal therapeutic target for gene therapy

  • The eye is a highly accessible and compact organ⁶,¹⁵
  • The eye can be easily targeted with limited systemic side effects¹²,¹⁵
  • Treatment can be delivered directly to the eye using a 1-time administration¹²,¹⁵
  • Wide range of delivery routes are being studied: intravitreal delivery, subretinal delivery, and suprachoroidal delivery¹⁵
  • Results are easily measurable with new imaging and functional assessment tools⁸,¹⁶

ACHM=achromatopsia; EMA=European Medicines Agency; FDA=Food and Drug Administration; LCA=Leber congenital amaurosis; RP=retinitis pigmentosa; USH=Usher syndrome; XLRP=X-linked retinitis pigmentosa.

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  • 1. Nuzbrokh Y, Ragi SD, Tsang SH. Gene therapy for inherited retinal diseases. Ann Transl Med. 2021;9(15):1278.
  • 2. Public Health – Union Register of medicinal products. Union Register of medicinal products for human use. Updated April 9, 2023. Accessed September 26, 2024. https://ec.europa.eu/health/documents/community-register/html/h1331.htm
  • 3. Méjécase C, Malka S, Guan Z, Slater A, Arno G, Moosajee M. Practical guide to genetic screening for inherited eye diseases. Ther Adv Ophthalmol. 2020;12:2515841420954592.
  • 4. Branham K, Schlegel D, Fahim AT, Jayasundera KT. Genetic testing for inherited retinal degenerations: triumphs and tribulations. Am J Med Genet C Semin Med Genet. 2020;184(3):571-577.
  • 5. Tuupanen S, Gall K, Sistonen J, et al. Prevalence of RPGR-mediated retinal dystrophy in an unselected cohort of over 5000 patients. Trans Vis Sci Technol. 2022;11(1):6.
  • 6. Martinez-Fernandez De La Camara C, Nanda A, Salvetti AP, Fischer MD, MacLaren RE. Gene therapy for the treatment of X-linked retinitis pigmentosa. Expert Opin Orphan Drugs. 2018;6(3):167-177.
  • 7. Kumaran N, Ali R, Tyler N, Bainbridge J, Michaelides M, Rubin GS. Validation of a vision-guided mobility assessment for RPE65-associated retinal dystrophy. Transl Vis Sci Technol. 2020;9(10):5.
  • 8. 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(3):247-259.
  • 9. LUXTURNA [package insert]. Spark Therapeutics, Inc; 2017.
  • 10. Gene therapy. ClinicalTrials.gov. Accessed September 26, 2024. https://clinicaltrials.gov/search?cond=gene%20therapy&term=inherited%20retinal%20disease&aggFilters=status:not%20rec%20act
  • 11. Lee JH, Wang JH, Chen J, et al. Gene therapy for visual loss: opportunities and concerns. Prog Retin Eye Res. 2018;68:31-53.
  • 12. Bakall B, Hariprasad SM, Klein KA. Emerging gene therapy treatments for inherited retinal diseases. Ophthalmic Surg Lasers Imaging Retina. 2018;49(7):472-478.
  • 13. Vázquez-Domínguez I, Garanto A, Collin RWJ. Molecular therapies for inherited retinal diseases—current standing, opportunities and challenges. Genes (Basel). 2019;10(9):654-684.
  • 14. Fry LE, Peddle CF, Barnard AR, McClements ME, MacLaren RE. RNA editing as a therapeutic approach for retinal gene therapy requiring long coding sequences. Int J Mol Sci. 2020;21(3):777.
  • 15. Moraru AD, Costin D, Iorga RE, Munteanu M, Moraru RL, Branisteanu DC. Current trends in gene therapy for retinal diseases (Review). Exp Ther Med. 2022;23(1):26.
  • 16. Lacy GD, Abalem MF, Musch DC, Jayasundera KT. Patient-reported outcome measures in inherited retinal degeneration gene therapy trials. Ophthalmic Genet. 2020;41(1):1-6.
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