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, CB Tara Moore

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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/mm 2 vs. 1837 ± 195.9 cells/mm 2, 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 μm 3 vs. 187,923 ± 28,575 μm 3; 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.

Original languageEnglish
Article number100150
JournalOphthalmology Science
Volume2
Issue number2
Early online date4 Apr 2022
DOIs
Publication statusPublished (in print/issue) - 30 Jun 2022

Keywords

  • Age-related macular degeneration
  • Angiogenesis
  • Choroidal neovascularization
  • Corneal vascularization
  • Ocular neovascularization

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