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Disease Category: autosomal dominant

Patient Population: 1,000 - 2,000

Known Clinical Trials: yes, 3 recruiting

Potential Treatment: Luxturna

Strategies to Preserve Eye Health: Lutein

Institution(s) Conducting Research: Perelman School of Medicine |

Children’s Hospital of Philadelphia (CHOP) | UOC Oculistica, Milan | 

Ospedale di Camposampiero | UOC Oculistica, Florence | Moorfields Eye Hospital | Kellogg Eye Center |







RPE65-associated inherited retinal diseases: consensus recommendations for eligibility to gene therapy

Inherited retinal dystrophy caused by confirmed biallelic mutations in the RPE65 gene, which encodes all-trans retinyl ester isomerase, an enzyme critical to the visual cycle, is a serious and sight-threatening autosomal recessive genetic disorder that causes a severe form of rod-cone mediated IRD that eventually progresses to complete blindness.

The effect of human gene therapy for RPE65-associated Leber’s congenital amaurosis on visual function: a systematic review and meta-analysis

Xue WangChaofeng YuRadouil T. TzekovYihua Zhu, and Wensheng Li | Orphanet Journal of Rare Diseases | Vol 15 (49) | 14 Feb 2020 |

RPE65-associated LCA (RPE65-LCA) is an inherited retinal degeneration caused by the mutations of RPE65 gene and gene therapy has been developed to be a promising treatment. This study aims to evaluate the association between changes in visual function and application of gene therapy in patients with RPE65-LCA.

Hiroyuki Morimura, Gerald A. Fishman, Sandeep A. Grover, Anne B. Fulton, Eliot L. Berson,  and

Thaddeus P. Dryja | PNAS | 17 Ma 1998 | Vol. 95 (6) |3088–3093 | doi: 10.1073/pnas.95.6.3088

To explore the possible role that defects in RPE65 might play in the etiology of retinal degenerations, we screened a large cohort of unrelated patients with retinitis pigmentosa or Leber congenital amaurosis for mutations. Because RPE65 is expressed specifically in the eye, the study focused on patients with nonsyndromic forms of these diseases. 

Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis

Advanced late-onset retinitis pigmentosa with dominant-acting D477G RPE65 mutation is responsive to oral synthetic retinoid therapy

Paul F KennaMarian M HumphriesAnna-Sophia Kiang, Philippe Brabet, Laurent Guillou, Ema Ozaki, Matthew Campbell, G Jane Farrar, Robert Koenekoop, Pete Humphries | BMJ Open Ophthalmology | 2020 | 5:e000462 | doi: 10.1136/bmjophth-2020-00046

Objectives No therapeutic interventions are currently available for autosomal dominant retinitis pigmentosa (adRP). An RPE65 Asp477Gly transition associates with late-onset adRP, reduced RPE65 enzymatic activity being one feature associated with this dominant variant. Our objective: to assess whether in a proof-of-concept study, oral synthetic 9 cis-retinyl acetate therapy improves vision in such advanced disease.

Voretigene Neparvovec in Retinal Diseases: A Review of the Current Clinical Evidence


Jie Gao, Rehan M Hussain, and Christina Y Weng | Clinical Ophthalmology | 13 Nov 2020 | Vol. 14 | 3855–3869 |doi: 10.2147/OPTH.S231804

Subretinal gene therapy trials began with the discovery of RPE65 variants and their association with Leber congenital amaurosis. The RPE65 protein is critical for the normal functioning of the visual phototransduction cascade. RPE65 gene knockout animal models were developed

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