Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives

Marina França Dias; Kwangsic Joo; Jessica A Kemp; Silvia Ligório Fialho; Armando da Silva Cunha Jr; Se Joon Woo; Young Jik Kwon

doi:10.1016/j.preteyeres.2017.10.004

Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives

Prog Retin Eye Res. 2018 Mar:63:107-131. doi: 10.1016/j.preteyeres.2017.10.004. Epub 2017 Oct 31.

Authors

Marina França Dias¹, Kwangsic Joo², Jessica A Kemp³, Silvia Ligório Fialho⁴, Armando da Silva Cunha Jr⁵, Se Joon Woo⁶, Young Jik Kwon⁷

Affiliations

¹ School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil; Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA.
² Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
³ Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA.
⁴ Pharmaceutical Research and Development, Ezequiel Dias Foundation, Belo Horizonte, Brazil.
⁵ School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil. Electronic address: armando@ufmg.br.
⁶ Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA; Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address: sejoon1@snu.ac.kr.
⁷ Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA; Department of Chemical Engineering and Materials Sciences, University of California, Irvine, CA, USA; Department of Biomedical Engineering, University of California, Irvine, CA, USA; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA. Electronic address: kwonyj@uci.edu.

PMID: 29097191
DOI: 10.1016/j.preteyeres.2017.10.004

Abstract

Retinitis Pigmentosa (RP) is a hereditary retinopathy that affects about 2.5 million people worldwide. It is characterized with progressive loss of rods and cones and causes severe visual dysfunction and eventual blindness in bilateral eyes. In addition to more than 3000 genetic mutations from about 70 genes, a wide genetic overlap with other types of retinal dystrophies has been reported with RP. This diversity of genetic pathophysiology makes treatment extremely challenging. Although therapeutic attempts have been made using various pharmacologic agents (neurotrophic factors, antioxidants, and anti-apoptotic agents), most are not targeted to the fundamental cause of RP, and their clinical efficacy has not been clearly proven. Current therapies for RP in ongoing or completed clinical trials include gene therapy, cell therapy, and retinal prostheses. Gene therapy, a strategy to correct the genetic defects using viral or non-viral vectors, has the potential to achieve definitive treatment by replacing or silencing a causative gene. Among many clinical trials of gene therapy for hereditary retinal diseases, a phase 3 clinical trial of voretigene neparvovec (AAV2-hRPE65v2, Luxturna) recently showed significant efficacy for RPE65-mediated inherited retinal dystrophy including Leber congenital amaurosis and RP. It is about to be approved as the first ocular gene therapy biologic product. Despite current limitations such as limited target genes and indicated patients, modest efficacy, and the invasive administration method, development in gene editing technology and novel gene delivery carriers make gene therapy a promising therapeutic modality for RP and other hereditary retinal dystrophies in the future.

Keywords: Gene therapy; Molecular genetics; Retinitis pigmentosa.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Biomedical Research
Clinical Studies as Topic
Genetic Therapy / methods*
Humans
Molecular Biology
Retinitis Pigmentosa / genetics*
Retinitis Pigmentosa / therapy*