Login (DCU Staff Only)
Login (DCU Staff Only)

DORAS | DCU Research Repository

Explore open access research and scholarly works from DCU

Advanced Search

COMP-Ang1: therapeutic potential of an engineered Angiopoietin-1 variant

Wallace, Robert G. orcid logoORCID: 0000-0002-1450-0634, Rochfort, Keith D. orcid logoORCID: 0000-0003-1198-5952, Barabas, Peter orcid logoORCID: 0000-0002-8166-3476, Curtis, Timothy M., Uehara, Hironori orcid logoORCID: 0000-0001-6133-4918, Ambati, Balamurali and Cummins, Phil (2021) COMP-Ang1: therapeutic potential of an engineered Angiopoietin-1 variant. Vascular Pharmacology, 141 . ISSN 1537-1891

Abstract
The Angiopoietin-1/2 system is an opportune target for therapeutic intervention in a wide range of vascular pathologies, particularly through its association with endothelium. The complex multi-domain structure of native human Angiopoietin-1 has hindered its widespread applicability as a therapeutic agent, prompting the search for alternative approaches to mimicking the Ang1:Tie2 signalling axis; a system with highly complex patterns of regulation involving multiple structurally similar molecules. An engineered variant, Cartilage Oligomeric Matrix Protein - Angiopoietin-1 (COMP-Ang1), has been demonstrated to overcome the limitations of the native molecule and activate the Tie2 pathway with several fold greater potency than Ang1, both in vitro and in vivo. The therapeutic efficacy of COMP-Ang1, at both the vascular and systemic levels, is evident from multiple studies. Beneficial impacts on skeletal muscle regeneration, wound healing and angiogenesis have been reported alongside renoprotective, anti-hypertensive and anti-inflammatory effects. COMP-Ang1 has also demonstrated synergy with other compounds to heighten bone repair, has been leveraged for potential use as a co-therapeutic for enhanced targeted cancer treatment, and has received considerable attention as an anti-leakage agent for microvascular diseases like diabetic retinopathy. This review examines the vascular Angiopoietin:Tie2 signalling mechanism, evaluates the potential therapeutic merits of engineered COMP-Ang1 in both vascular and systemic contexts, and addresses the inherent translational challenges in moving this potential therapeutic from bench-to- bedside.
Metadata
Item Type:Article (Published)
Refereed:Yes
Additional Information:Article number: 101542
Uncontrolled Keywords:Endothelial; COMP-Ang1; Tie2 ;Therapeutic Vascular
Subjects:Medical Sciences > Pharmacology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Research Initiatives and Centres > National Institute for Cellular Biotechnology (NICB)
Publisher:Elsevier
Official URL:https://dx.doi.org/10.1016/j.vph.2021.106919
Copyright Information:© 2020 The Authors. Open Access (CC BY-NC-ND 4.0)
Funders:Science Foundation Ireland US-Ireland R&D Partnership Programme (PMC, 14/US/B3116), National Institute of Health RO1 (BKA, RO1-EY026029), Northern Ireland Health and Social Care R&D Division (TC, STL/4748/13), Medical Research Council (TC, MC_PC_15026)
ID Code:27861
Deposited On:14 Oct 2022 11:25 by Thomas Murtagh . Last Modified 14 Oct 2022 11:52
Documents

Full text available as:

[thumbnail of 1-s2.0-S1537189121000914-main.pdf]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB
Downloads

Downloads

Downloads per month over past year

Archive Staff Only: edit this record