Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders
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-mo...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-06-01
|
| Series: | Ophthalmology Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666914522000392 |
| _version_ | 1818218855307149312 |
|---|---|
| author | Gideon Obasanmi, PhD M. Andrew Nesbit, PhD Diego Cobice, PhD Logan Mackay, PhD Stuart McGimpsey, MBBCh, BAO Mark Wappett, MRes Aaron N. Cranston, PhD Tara C.B. Moore, PhD |
| author_facet | Gideon Obasanmi, PhD M. Andrew Nesbit, PhD Diego Cobice, PhD Logan Mackay, PhD Stuart McGimpsey, MBBCh, BAO Mark Wappett, MRes Aaron N. Cranston, PhD Tara C.B. Moore, PhD |
| author_sort | Gideon Obasanmi, PhD |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T07:30:23Z |
| format | Article |
| id | doaj.art-6440abd86eb14cf8aa97dea51c7fb7fa |
| institution | Directory Open Access Journal |
| issn | 2666-9145 |
| language | English |
| last_indexed | 2024-12-12T07:30:23Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ophthalmology Science |
| spelling | doaj.art-6440abd86eb14cf8aa97dea51c7fb7fa2022-12-22T00:33:02ZengElsevierOphthalmology Science2666-91452022-06-0122100150Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye DisordersGideon Obasanmi, PhD0M. Andrew Nesbit, PhD1Diego Cobice, PhD2Logan Mackay, PhD3Stuart McGimpsey, MBBCh, BAO4Mark Wappett, MRes5Aaron N. Cranston, PhD6Tara C.B. Moore, PhD7Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, United KingdomBiomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, United KingdomBiomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, United KingdomScottish Instrumentation and Research Centre for Advanced Mass Spectrometry (SIRCAMS), School of Chemistry, University of Edinburgh, Edinburgh, United KingdomMater Infirmorum Hospital (Belfast Health and Social Care Trust), Belfast, United KingdomCentre for Precision Therapeutics, Almac Discovery Ltd., Belfast, United KingdomCentre for Precision Therapeutics, Almac Discovery Ltd., Belfast, United Kingdom; Correspondence: Aaron N. Cranston, PhD, Centre for Precision Therapeutics, Almac Discovery Ltd., 97 Lisburn Road, Belfast, BT9 7AE, United Kingdom.Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, United Kingdom; Tara C. B. Moore, PhD, Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Cromore Road, BT52 1SA, Coleraine, United Kingdom.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.http://www.sciencedirect.com/science/article/pii/S2666914522000392Age-related macular degenerationAngiogenesisChoroidal neovascularizationCorneal vascularizationOcular neovascularization |
| spellingShingle | Gideon Obasanmi, PhD M. Andrew Nesbit, PhD Diego Cobice, PhD Logan Mackay, PhD Stuart McGimpsey, MBBCh, BAO Mark Wappett, MRes Aaron N. Cranston, PhD Tara C.B. Moore, PhD Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders Ophthalmology Science Age-related macular degeneration Angiogenesis Choroidal neovascularization Corneal vascularization Ocular neovascularization |
| title | Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders |
| title_full | Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders |
| title_fullStr | Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders |
| title_full_unstemmed | Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders |
| title_short | Successful Proof-of-Concept for Topical Delivery of Novel Peptide ALM201 with Potential Usefulness for Treating Neovascular Eye Disorders |
| title_sort | successful proof of concept for topical delivery of novel peptide alm201 with potential usefulness for treating neovascular eye disorders |
| topic | Age-related macular degeneration Angiogenesis Choroidal neovascularization Corneal vascularization Ocular neovascularization |
| url | http://www.sciencedirect.com/science/article/pii/S2666914522000392 |
| work_keys_str_mv | AT gideonobasanmiphd successfulproofofconceptfortopicaldeliveryofnovelpeptidealm201withpotentialusefulnessfortreatingneovasculareyedisorders AT mandrewnesbitphd successfulproofofconceptfortopicaldeliveryofnovelpeptidealm201withpotentialusefulnessfortreatingneovasculareyedisorders AT diegocobicephd successfulproofofconceptfortopicaldeliveryofnovelpeptidealm201withpotentialusefulnessfortreatingneovasculareyedisorders AT loganmackayphd successfulproofofconceptfortopicaldeliveryofnovelpeptidealm201withpotentialusefulnessfortreatingneovasculareyedisorders AT stuartmcgimpseymbbchbao successfulproofofconceptfortopicaldeliveryofnovelpeptidealm201withpotentialusefulnessfortreatingneovasculareyedisorders AT markwappettmres successfulproofofconceptfortopicaldeliveryofnovelpeptidealm201withpotentialusefulnessfortreatingneovasculareyedisorders AT aaronncranstonphd successfulproofofconceptfortopicaldeliveryofnovelpeptidealm201withpotentialusefulnessfortreatingneovasculareyedisorders AT taracbmoorephd successfulproofofconceptfortopicaldeliveryofnovelpeptidealm201withpotentialusefulnessfortreatingneovasculareyedisorders |