[Inherited retinal dystrophy: first results of RPE65 gene replacement therapy in Russia].

Area of Science:

• Ophthalmology
• Genetics
• Medical Diagnostics

Background:

• Hereditary retinal diseases (HRD) are a group of disabling conditions often considered untreatable.
• Biallelic mutations in the RPE65 gene cause specific inherited retinal dystrophies (IRD), including Leber amaurosis type 2.
• Advances in genetic diagnostics and gene therapy offer new hope for patients with previously untreatable HRD.

Purpose of the Study:

• To outline the interdisciplinary diagnostic approach for patients with hereditary retinal diseases.
• To present the initial outcomes of gene replacement therapy in Russian patients with RPE65-associated IRD.
• To evaluate the efficacy of Voretigene neparvovec in treating Leber amaurosis type 2.

Main Methods:

• A cohort of six children (5-15 years old) diagnosed with Leber amaurosis type 2 was studied.
• Comprehensive diagnostics included clinical, instrumental, and molecular-genetic evaluations.
• Genetic diagnosis was confirmed via high-performance parallel sequencing and Sanger sequencing for family segregation analysis.

Main Results:

• The first group of Russian patients with orphan IRD received subretinal injections of Voretigene neparvovec (12 eyes).
• Patients underwent regular follow-up examinations at 1, 3, 6, and 12 months post-treatment.
• The initial 3-month follow-up data demonstrated irrefutable positive results in all treated patients.

Conclusions:

• The study highlights the necessity of updating diagnostic algorithms in ophthalmic practice for HRD.
• Integrated diagnostic methods enable etiotropic treatment for previously untreatable disabling eye conditions.
• Voretigene neparvovec has shown significant early positive effects in Russian patients with RPE65-mutated IRD.