Abstract: PO1408
Effect of ANG-3070 in the Passive Heymann Nephritis Rat Model of Primary Proteinuric Kidney Disease
Session Information
- Glomerular Diseases: Fibrosis and Extracellular Matrix
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Pedigo, Christopher, Angion Biomedica Corp, Uniondale, New York, United States
- Hu, Zhijian, Angion Biomedica Corp, Uniondale, New York, United States
- Zhou, Ping, Angion Biomedica Corp, Uniondale, New York, United States
- McCormack, Siobhan, Angion Biomedica Corp, Uniondale, New York, United States
- Li, Jingsong, Angion Biomedica Corp, Uniondale, New York, United States
- Prakash, Natalia, Angion Biomedica Corp, Uniondale, New York, United States
- Pellicano, Anthony, Angion Biomedica Corp, Uniondale, New York, United States
- Narayan, Prakash, Angion Biomedica Corp, Uniondale, New York, United States
- Goldberg, Itzhak D., Angion Biomedica Corp, Uniondale, New York, United States
Background
Primary proteinuric kidney diseases (PPKD) as a group are an important cause of end-stage kidney disease (ESKD). Many receptor tyrosine kinases, including platelet-derived growth factor receptor (PDGFR), contribute to the progression of PPKDs to ESKD. ANG-3070 is a novel and proprietary inhibitor of multiple tyrosine kinases including PDGFR. This study evaluated the effects of ANG-3070 in a passive Heymann’s nephritis (PHN) rat model of membranous glomerulopathy.
Methods
Male Sprague Dawley rats (300g) were administered anti-FX1A serum. Treatment groups included 15mg/kg ANG-3070 (n=11), Vehicle (n=11) and Sham (n=5). Animals were dosed orally, twice daily, for 12 weeks, and 24-hour urines were collected biweekly. At sacrifice, kidney tissue was harvested.
Results
Twelve-week treatment with orally dosed ANG-3070 significantly reduced the protein to creatinine ratio as compared to Vehicle (mg/mg; 5.3 vs 9.4; p<0.05). It also led to a significant reduction in total kidney hydroxyproline content (μg/kidney; 952 vs. 1416; p<0.05), indicating a reduction in fibrotic tissue. When periodic acid-Schiff staining from kidney sections were evaluated for glomerular damage by two blinded observers on a scale of 0 (normal/no injury) to 4 (severe injury), ANG-3070 significantly reduced glomerular damage (1.7 vs. 2.6; p<0.05), indicating a reduction in glomerulosclerosis. The evaluation of PDGFRβ levels from total kidney lysates by Western Blot indicated an increase in the Vehicle treated group compared to Sham (PDGFRβ/GAPDH; 2.6 vs 0.7, p<0.05). ANG-3070 treatment significantly reduced these levels when compared to Vehicle (PDGFRβ/GAPDH; 1.0 vs 2.6, p<0.05), which was comparable to the levels observed in the Sham group.
Conclusion
Twice-daily oral administration of the novel tyrosine kinase inhibitor ANG-3070 reduces proteinuria, renal fibrosis, glomerulosclerosis and PDGFRβ expression levels in a rat model of PHN. These data suggest ANG-3070 may be an effective treatment in PPKDs.
Funding
- Other U.S. Government Support –