Personalized therapeutic strategies for patients with retinitis pigmentosa

Abstract

Introduction Retinitis pigmentosa (RP) encompasses many different hereditary retinal degenerations that are caused by a vast array of different gene mutations and have highly variable disease presentations and severities. This heterogeneity poses a significant therapeutic challenge, although an answer may eventually be found through two recent innovations: induced pluripotent stem cells (iPSCs) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome editing. Areas covered This review discusses the wide-ranging applications of iPSCs and CRISPR–including disease modelling, diagnostics and therapeutics – with an ultimate view towards understanding how these two technologies can come together to address disease heterogeneity and orphan genes in a novel personalized medicine platform. An extensive literature search was conducted in PubMed and Google Scholar, with a particular focus on high-impact research published within the last 1 – 2 years and centered broadly on the subjects of retinal gene therapy, iPSC-derived outer retina cells, stem cell transplantation and CRISPR/Cas gene editing. Expert opinion For the retinal pigment epithelium, autologous transplantation of gene-corrected grafts derived from iPSCs may well be technically feasible in the near future. Photoreceptor transplantation faces more significant unresolved technical challenges but remains an achievable, if more distant, goal given the rapid pace of advancements in the field.

Protective effect of sulforaphane against retinal degeneration in the Pde6rd10 mouse model of retinitis pigmentosa

“…Although various treatments have been used to protect retinal cells, such as antioxidants, gene or stem cell therapy,(1-3) no effective medications are available for RP treatment due to the limited therapeutic benefits or side effects. (4)…”

Structural modeling of a novel SLC38A8 mutation that causes foveal hypoplasia

“…; Zheng et al. ; Pyo Park et al ). Precision medicine requires highly accurate phenotype–genotype correlations that could be enhanced with new imaging and DNA sequencing modalities.…”

“…The recent success of regenerative medicine approaches for retinal disease makes accurate and precise diagnosis even more important in children with inherited disease, who may become candidates for gene and cell therapies (Zhou et al 1989;Li et al 2014Li et al , 2016Tsang et al 2014;Lin et al 2015;Zheng et al 2015;Pyo Park et al 2013). Precision medicine requires highly accurate phenotype-genotype correlations that could be enhanced with new imaging and DNA sequencing modalities.…”

The natural retinoprotectant chrysophanol attenuated photoreceptor cell apoptosis in an N-methyl-N-nitrosourea-induced mouse model of retinal degenaration

“…RP commonly results in vision loss, especially in patients who develop RP in adolescence or infancy. Therefore, visual acuity is disrupted during the early stages of RP, resulting in significantly higher healthcare costs and disability-adjusted life years for these patients6. Although RP affects millions of individuals worldwide, there are no therapies currently approved for the treatment of this disease.…”