Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders

Gideon Obasanmi; M Andrew Nesbit; Diego Cobice; Logan Mackay; Stuart McGimpsey; Mark Wappett; Aaron N Cranston; Tara C B Moore

doi:10.1016/j.xops.2022.100150

Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders

Ophthalmol Sci. 2022 Apr 4;2(2):100150. doi: 10.1016/j.xops.2022.100150. eCollection 2022 Jun.

Authors

Gideon Obasanmi¹, M Andrew Nesbit¹, Diego Cobice¹, Logan Mackay², Stuart McGimpsey³, Mark Wappett⁴, Aaron N Cranston⁴, Tara C B Moore¹

Affiliations

¹ Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom.
² Scottish Instrumentation and Research Centre for Advanced Mass Spectrometry (SIRCAMS), School of Chemistry, University of Edinburgh, Edinburgh, United Kingdom.
³ Mater Infirmorum Hospital (Belfast Health and Social Care Trust), Belfast, United Kingdom.
⁴ Centre for Precision Therapeutics, Almac Discovery Ltd., Belfast, United Kingdom.

Abstract

Purpose: To evaluate the therapeutic benefit of a novel peptide, ALM201, in ocular pathologic vascularization.

Design: Experimental study in mouse, rat, and rabbit animal models.

Participants: Ten-week-old Lister Hooded male rats, 8-week-old Brown Norway male rats, 9-day-old C57BL/6J mice, and 12-month-old New Zealand male rabbits.

Methods: Corneal vascularization was scored for vessel density and vessel distance to suture in a rat corneal suture model. Ocular penetration and biodistribution were evaluated by matrix-assisted laser desorption/ionization mass spectrometry imaging after topical ALM201 application to rabbit eyes. A mouse choroidal sprouting assay, with aflibercept as positive control, was used to evaluate choroidal neovascularization (CNV) in the posterior segment tissue. Efficacy of topical ALM201 was assessed using a rat laser CNV model of neovascular age-related macular degeneration.

Main outcome measures: Clinical scoring and histologic analysis of vascularized corneas, sprouting area, lesion size, and vessel leakiness in posterior segments.

Results: Assessment of ALM201 treatment in the rat corneal suture model showed a significant decrease in vessel density (P = 0.0065) and vessel distance to suture (P = 0.021) compared with vehicle control (phosphate-buffered saline [PBS]). Infiltration of inflammatory cells into the corneal stroma also was reduced significantly compared with PBS (724.5 ± 122 cells/mm² vs. 1837 ± 195.9 cells/mm², respectively; P = 0.0029). Biodistribution in rabbit eyes confirmed ALM201 bioavailability in anterior and posterior ocular segments 1 hour after topical instillation. ALM201 treatment significantly suppressed choroid vessel sprouting when compared with PBS treatment (44.5 ± 14.31 pixels vs. 120.9 ± 33.37 pixels, respectively; P = 0.04) and was not inferior to aflibercept (65.63 ± 11.86 pixels; P = 0.7459). Furthermore, topical ALM201 significantly improved vessel leakiness (leakage scores: 2.1 ± 0.7 vs. 2.9 ± 0.1; P = 0.0274) and lesion size (144,729 ± 33,239 μm³ vs. 187,923 ± 28,575 μm³; P = 0.03) in the rat laser CNV model when compared with topical PBS vehicle.

Conclusions: ALM201 is a promising novel molecule with anti-inflammatory and antivascularization activity and is a strong candidate to meet the clinical need of a new, topically delivered therapeutic agent for treating inflammation and pathologic vascularization in the anterior and posterior segments of the eye.

Keywords: AMD, age-related macular degeneration; Age-related macular degeneration; Angiogenesis; CNV, choroidal neovascularization; CV, corneal vascularization; Choroidal neovascularization; Corneal vascularization; HRA, Heidelberg retinal angiograph; Ocular neovascularization; PBS, phosphate-buffered saline; ROI, region of interest; VEGF, vascular endothelial growth factor; nAMD, neovascular age-related macular degeneration.