{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:39:03Z","timestamp":1784770743977,"version":"3.55.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":69,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust Senior Fellowship in Clinical Science","award":["212252\/Z\/18\/Z"],"award-info":[{"award-number":["212252\/Z\/18\/Z"]}]},{"name":"Rebecca L. Cooper Foundation","award":["PG2019449"],"award-info":[{"award-number":["PG2019449"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Complement activation contributes to kidney damage in many types of glomerulonephritis and complement inhibition therapy is approved for IgA nephropathy and C3 glomerulopathy. However, inhibition is not specific to the kidney resulting in unnecessary systemic complement inhibition and increased infection risk. To develop an effective inhibitor of glomerular complement we combined complement factor H-related protein 5 (FHR51-9), which binds to glomerular complement C3, with the complement regulatory domains of the key negative regulator of C3 activation complement factor H (FH1-5). One week after adeno-associated virus (AAV) mediated expression of the FHR51-9FH1-5 fusion protein in factor H (FH)-deficient mice, glomerular C3b\/iC3b\/C3c was significantly reduced and properdin resolved completely compared to controls. There was no change to circulating C3 levels and FHR51-9FH1-5 was detected in glomeruli in association with C3d. Six and twenty weeks after AAV8-FHR51-9FH1-5 treatment in hFH-FHR5mut mice (a mouse model of CFHR5 nephropathy) glomerular C3b\/iC3b\/C3c, C3d, and C5 were significantly reduced and properdin resolved completely compared to controls. Pre-administration of AAV-FHR51-9FH1-5 also ameliorated abnormal glomerular C3b\/iC3b\/C3c, C3d, C5, and properdin in a triggered CFHR5 nephropathy model. In vitro FHR51-9FH1-5 showed dose-dependent binding to surface-immobilized C3, C3b, iC3b, and C3d; factor I cofactor activity; and reduced C3a generation in an alternative pathway convertase assay. Taken together, the FHR51-9FH1-5 protein reduced glomerular C3 in experimental models of C3 glomerulopathy driven by either FH deficiency or mutated FHR5. These preclinical data indicate that FHR51-9FH1-5 protein represents a novel treatment strategy for complement-mediated kidney disease.<\/jats:p>","DOI":"10.1093\/cei\/uxag015","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T12:21:56Z","timestamp":1773058916000},"source":"Crossref","is-referenced-by-count":1,"title":["A novel fusion protein reduces kidney complement in experimental C3 glomerulopathy"],"prefix":"10.1093","volume":"220","author":[{"given":"Talat H","family":"Malik","sequence":"first","affiliation":[{"name":"Centre for Inflammatory Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Kwiatkowska","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah J","family":"Lomax-Browne","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte M","family":"Bottomley","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Bright","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang Sung","family":"Tean","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet K","family":"Akturk","sequence":"additional","affiliation":[{"name":"Centre for Inflammatory 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