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Current therapies, although successful, are prone to high levels of patient non\u2010response and a loss of efficacy over time, indicating the need to explore other therapeutic avenues. We have shown that an interaction between syndecan\u20102 and the tyrosine phosphatase receptor CD148 (RTP Type J) results in the ablation of angiogenesis. Here we exploit this pathway to develop a peptide activator of CD148 as a therapy for neovascular age\u2010related macular degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We tested a peptide (QM107) derived from syndecan\u20102 in a variety of angiogenesis models and a pre\u2010clinical model of neovascular age\u2010related macular degeneration. We assessed the toxicological and inflammatory profiles of QM107 and its stability in vitreous humour.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      QM107 inhibits angiogenesis in\n                      <jats:italic>ex vivo<\/jats:italic>\n                      sprouting assays and disrupts endothelial microcapillary formation via inhibition of cell migration. QM107 acts through CD148, leading to changes in GSK3A phosphorylation and\n                      <jats:italic>\u03b2<\/jats:italic>\n                      1 integrin activation. QM107 elicits a negligible inflammatory response and exhibits limited toxicity in cultured cells, and is stable in vitreous humour. Finally, we show proof of concept that QM107 blocks angiogenesis\n                      <jats:italic>in vivo<\/jats:italic>\n                      using a model of neovascular age\u2010related macular degeneration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>We have developed a CD148 activating peptide which shows promise in inhibiting angiogenesis in models of neovascular age\u2010related macular degeneration. This treatment could either represent an alternative or augment existing therapies, and owing to its distinct mode of action be used in patients who do not respond to existing treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.17362","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:25:21Z","timestamp":1729470321000},"page":"951-968","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["QM107, a novel CD148 (RTP Type J) activating peptide therapy for treating neovascular age\u2010related macular degeneration"],"prefix":"10.1111","volume":"182","author":[{"given":"Samantha","family":"Arokiasamy","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela J. 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