A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy

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Title: A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy
Authors: Sulaiman, Rania S.
Merrigan, Stephanie
Quigley, Judith
Kennedy, Breandán
et al.
Permanent link: http://hdl.handle.net/10197/8346
Date: 5-May-2016
Abstract: Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These diseases cause irreversible vision loss, and provide a significant health and economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% of patients are non-responsive to these drugs and they are associated with ocular and systemic side effects. Therefore, there is a need for small molecule ocular angiogenesis inhibitors to complement existing therapies. We examined the safety and therapeutic potential of SH-11037, a synthetic derivative of the antiangiogenic homoisoflavonoid cremastranone, in models of ocular neovascularisation. SH-11037 dose-dependently suppressed angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. Additionally, intravitreal SH-11037 (1 μM) significantly reduced choroidal neovascularisation (CNV) lesion volume in the laser-induced CNV mouse model, comparable to an anti-VEGF antibody. Moreover, SH-11037 synergised with anti-VEGF treatments in vitro and in vivo. Up to 100 μM SH-11037 was not associated with signs of ocular toxicity and did not interfere with retinal function or pre-existing retinal vasculature. SH-11037 is thus a safe and effective treatment for murine ocular neovascularisation, worthy of further mechanistic and pharmacokinetic evaluation.
Type of material: Journal Article
Publisher: Nature Publishing Group
Copyright (published version): 2016 the Authors
Keywords: Pharmacodynamics;Angiogenesis;Experimental models of disease;Macular degeneration;Retinal diseases
DOI: 10.1038/srep25509
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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