Rationale and Design for a Phase 1 Study of N-Acetylmannosamine for Primary Glomerular Diseases

Abstract

INTRODUCTION: -acetylmannosamine (ManNAc), the uncharged precursor of sialic acid, ameliorates glomerular pathology in different models of glomerular disease. METHODS: Here we explore the sialylation status of kidney biopsies obtained from 27 subjects with various glomerular diseases using lectin histochemistry. RESULTS: We identified severe glomerular hyposialylation in 26% of the biopsies. These preliminary findings suggest that this condition may occur relatively frequently and may be a novel target for therapy. We describe the background, rationale, and design of a phase 1 study to test safety, tolerability, and pharmacokinetics of ManNAc in subjects with primary podocyte diseases. CONCLUSION: -acetylglucosamine (GlcNAc) 2-epimerase/ManNAc kinase (GNE) myopathy, a disorder of impaired sialic acid synthesis. Using previous preclinical and clinical data, we propose to test ManNAc therapy for subjects with primary glomerular diseases. Even though the exact mechanisms, affected cell types, and pathologic consequences of glomerular hyposialylation need further study, treatment with this physiological monosaccharide could potentially replace or supplement existing glomerular diseases therapies.