MCP-1/CCR2 System as Therapeutic Target

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Whether the MCP-1/CCR2 system is a potential new target for treatment in humans remains to be proven, but there are several clinical trials currently testing this hypothesis. A Phase 2 multicenter study is currently recruiting type 2 diabetic patients with overt nephropathy to evaluate both the efficacy and safety of the CCR2/5 antagonist PF-04634817 that has been previously shown to be safe in healthy subjects. CCX140-B, a specific CCR2 antagonist, has been shown to be safe in a Phase 2 clinical trial in type 2 diabetic patients with normal renal function [111] and is currently tested in two European clinical trials for safety and efficacy in type 2 diabetic patients with DN. A number of Phase 1 and Phase 2 clinical trials are ongoing to investigate the potential therapeutic benefit of anti-MCP-1 Spiegelmer NOX-E36 (an anti-MCP-1-enantiomeric RNA aptamer) [112] in DN. A randomized, double blind, placebo-controlled Phase 2a study has been recently completed and findings reported at the Late Breaking Clinical Trials Symposium at the 2014 ERA-EDTA Conference. These unpublished results show that NOX-36 (emapticap pegol) added to standard therapy, including RAS blockade, is well tolerated and reduces both albumin/creatinine ratio and HbA1c in type 2 diabetics with albuminuria. There is thus increasing interest in this area of research and targeting the MCP-1/CCR2 system appears a promising novel therapeutic approach.