Optimal Efficacy and Safety of Humanized Anti-Scg3 Antibody to Alleviate Oxygen-Induced Retinopathy.

Ye He,Chang Dai,Xiaorong Li,Hong Tian,Keith A Webster,Wei Li,Rong Wen

doi:10.3390/ijms23010350

Abstract

The retinopathy of prematurity (ROP), a neovascular retinal disorder presenting in premature infants, is the leading causes of blindness in children. Currently, there is no approved drug therapy for ROP in the U.S., highlighting the urgent unmet clinical need for a novel therapeutic to treat the disease. Secretogranin III (Scg3) was recently identified as a disease-selective angiogenic factor, and Scg3-neutralizing monoclonal antibodies were reported to alleviate pathological retinal neovascularization in mouse models. In this study, we characterized the efficacy and safety of a full-length humanized anti-Scg3 antibody (hAb) to ameliorate retinal pathology in oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, by implementing histological and functional analyses. Our results demonstrate that the anti-Scg3 hAb outperforms the vascular endothelial growth factor inhibitor aflibercept in terms of efficacy and safety to treat OIR mice. Our findings support the development of anti-Scg3 hAb for clinical application.

Highlights

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder primarily occurring in premature infants and is one of the leading causes of blindness in children [1]
Our findings demonstrated that Scg3-neutralizing monoclonal antibodies mitigated pathological retinal neovascularization (RNV) in oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, with minimal adverse effects on the developing retina and other organ systems [6,13]
Analyses of retinal vessels stained with Alexa Fluor 488-conjugated isolectin B4 (AF488-IB4) at P17 revealed a decrease in pathological RNV in mice treated with anti-Scg3 humanized anti-Scg3 antibody (hAb)

Summary

Introduction

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder primarily occurring in premature infants and is one of the leading causes of blindness in children [1]. Current treatments for ROP include cryotherapy and laser photocoagulation for the ablation of avascular area. These treatments often damage the retina by destroying the peripheral vision in attempts to preserve the central vision and do not address the underlying cause of pathological RNV. Anti-VEGF drugs developed for other ocular neovascular diseases, such as wet age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion, have been investigated for ROP therapy. Clinical studies found that ROP infants treated with the anti-VEGF drug bevacizumab were associated with lower motor scores and higher rates of severe neurodevelopmental disability in comparison with laser treatment 18 months post treatment [11]. An urgent unmet clinical need is to develop an effective and safe anti-angiogenic therapy for the disease

Methods

Results

Conclusion