[PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis]
>>Nephrol Dial Transplant. 2007 Feb 17; [Epub ahead of print]
PDGF-D inhibition by CR002 ameliorates tubulointerstitial fibrosis following experimental glomerulonephritis.
Boor P, Konieczny A, Villa L, Kunter U, van Roeyen CR, Larochelle WJ, Smithson G, Arrol S, Ostendorf T, Floege J.
Division of Nephrology, RWTH University of Aachen, Germany, Department of Clinical and Experimental Pharmacology, Slovak Medical University, Bratislava, Slovakia and CuraGen Corporation, Branford, Connecticut, USA.
BACKGROUND: Arresting or regressing kidney scarring is of major clinical relevance. Platelet-derived growth factor D (PDGF-D) is widely expressed in fibrotic kidneys. Administration of the PDGF-D neutralizing fully human monoclonal antibody CR002 in the acute phase of progressive anti-Thy 1.1 glomerulonephritis reduced glomerular and secondary tubulointerstitial damage. METHODS: Using this model, we now assessed the effects of CR002 (n = 15) vs irrelevant control IgG (n = 17) administered on days 17, 28 and 35 after disease induction, i.e. after acute glomerular damage had subsided. Results. In vitro, CR002 inhibited the PDGF-D- but not the PDGF-B-induced proliferation of rat renal fibroblasts. Following the first CR002 injection on day 17, exposure to therapeutic levels was maintained until day 49. Proteinuria in the CR002-treated group was transiently reduced between days 49 and 77 (-19 to -23% in comparison with the controls; P < 0.05). On day 100, CR002 treatment reduced the number of rats that had doubled their serum creatinine (CR002: 40 vs controls: 71%; P < 0.05). Compared with controls, the CR002 animals, on day 100, significantly lowered glomerular expression of vimentin and collagens as well as tubulointerstitial damage scores, interstitial fibrosis, vimentin and cortical PDGF-D mRNA levels. CONCLUSIONS: PDGF-D antagonism, even after the phase of acute glomerular damage, exerts beneficial effects on the course of tubulointerstitial damage, i.e. the final common pathway of most renal diseases.<<
Extends the the data from the previous study some.
Cheers, Tuck |
