A novel fusion protein reduces kidney complement in experimental C3 glomerulopathy - PubMed
12 hours ago
- #Complement
- #Therapy
- #Glomerulonephritis
- A novel fusion protein, FHR51-9FH1-5, reduces kidney complement in experimental C3 glomerulopathy.
- The fusion protein combines complement factor H-related protein 5 (FHR51-9) with complement factor H (FH1-5) regulatory domains.
- AAV-mediated expression of FHR51-9FH1-5 significantly reduced glomerular C3b/iC3b/C3c and resolved properdin in factor H-deficient mice.
- No change in circulating C3 levels was observed, and FHR51-9FH1-5 was detected in glomeruli associated with C3d.
- In hFH-FHR5mut mice, the fusion protein reduced glomerular C3b/iC3b/C3c, C3d, and C5, and resolved properdin.
- Pre-administration of AAV-FHR51-9FH1-5 ameliorated abnormal glomerular complement in a triggered CFHR5 nephropathy model.
- In vitro, FHR51-9FH1-5 showed dose-dependent binding to C3, C3b, iC3b, and C3d, and reduced C3a generation.
- The fusion protein represents a novel treatment strategy for complement-mediated kidney disease.