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

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.

• Authors: Gideon Obasanmi, M Andrew Nesbit, Diego Cobice, Logan Mackay, Stuart McGimpsey, Mark Wappett, Aaron N Cranston, Tara C B Moore
• Journal: Ophthalmology science (Ophthalmol Sci) Vol. 2 Issue 2 Pg. 100150 (Jun 2022) ISSN: 2666-9145 [Electronic] Netherlands
• PMID: 36249680 (Publication Type: Journal Article)
• Copyright: © 2022 by the American Academy of Ophthalmology.