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

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PURPOSE

To present the main aspects of interdisciplinary diagnostics of patients with hereditary retinal diseases and the first results of the follow-up of patients with inherited retinal dystrophies (IRD) caused by biallelic mutations in the gene RPE65 after gene replacement therapy in Russia.

MATERIAL AND METHODS

The cohort of patients consisted of six children (5-15 years old) with the diagnosis of Leber amaurosis type 2. All patients underwent a multi-disciplinary examination using conventional clinical, instrumental and molecular-genetic methods. Genetic diagnosis was established based on the results of two-stage DNA diagnostics using high-performance parallel sequencing of a custom panel and family segregation analysis by Sanger sequencing.

RESULTS

In the Research Centre for Medical Genetics the first group of Russian patients with an orphan inherited retinal disease was verified, they underwent subretinal injection of the gene replacement drug Voretigene neparvovec (12 eyes) in the Helmholtz National Medical Research Center of Eye Diseases. According to the regulated terms of monitoring gene therapy patients, they were examined in the Research Centre for Medical Genetics after 1, 3, 6 and 12 months, and then once per year. Thus, the available data allows us to analyze the first results 3 months after the treatment.

CONCLUSION

The presented data on inherited retinal dystrophies caused by biallelic mutations in the RPE65 gene emphasize the need to change the diagnostic algorithm in the ophthalmic practice. The use of clinical instrumental and molecular genetic diagnostic methods makes it possible to apply etiotropic treatment to patients with a disabling disease that was previously considered untreatable. The gene replacement drug Voretigene neparvovec registered in Russia showed irrefutable first positive results in all targeted patients.

Keywords:

inherited retinal dystrophy

gene therapy

retina

genetics

Voretigene neparvovec

Luxturna

Leber amaurosis

retinitis pigmentosa

epidemiology

monitoring

Authors:

Kadyshev V.V.

N.P. Bochkov Research Centre for Medical Genetics

ORCID: 0000-0001-7765-3307

Zolnikova I.V.

N.P. Bochkov Research Centre for Medical Genetics;
Helmholtz National Medical Research Center of Eye Diseases

ORCID: 0000-0001-7264-396X

Khalanskaya O.V.

N.P. Bochkov Research Centre for Medical Genetics

ORCID: 0000-0003-2708-9220

Stepanova A.A.

N.P. Bochkov Research Centre for Medical Genetics

ORCID: 0000-0003-0416-8137

Kutsev S.I.

N.P. Bochkov Research Centre for Medical Genetics

ORCID: 0000-0002-3133-8018

Received:

07.05.2022

Accepted:

07.07.2022

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