Redox-active clearance of Highly Glycated RBCs: A new Frontier for the Treatment of Diabetic Vasculopathies

Abstract

Objective On the global scale, 24-54% of the diabetic patients do not reach Quality Assurance (QA) target hemoglobin A1c (HbA1c) values, despite Standard of Care (SOC) treatment with glucose-lowering drugs. An alternative approach to lower highly glycated Red Blood Cells (RBCs) directly is needed to reduce the risk for development of diabetic vascular complications. HbA1c > 7.0% (53.0 mmol/mol) is associated with increasing incidence of vascular pathologies and inflammation. We tested an alternative approach to avoid pathological effects of excess glycation via direct redox-active clearance of highly glycated Red Blood Cells (RBCs) with the objective to rapidly terminate the trigger of endothelial damage and thereby to reduce the risk for development/ progression of diabetic vascular complications. We report results from a controlled clinical trial in 20 patients with high HbA1c, elevated Neutrophil-Lymphocyte Ratio (NLR) values and diabetic foot ulcer (DFU), using the chlorite-based drug WF10. HbA1c was observed, with 83% of the patients achieving HbA1c ≤ 7.0% (53.0 mmol/ mol), versus 25% in the SOC group. Lowering HbA1c to Fasting Blood Sugar- (FBS-) ratios and changes in hematological markers indicate a removal of highly glycated, pre-hemolytic RBCs by the drug. In patients with peripheral artery disease (PAD), mean Ankle Branchial Index- (ABI-) values improved from 0.83 to 1.01. The median