ManNAc is an intermediary in cellular sialic acid biosynthesis generated by the GNE protein, which is the defective protein in GNE Myopathy. Preclinical data suggest that supplementation of ManNAc to cellular models with dysfunctional GNE protein bypasses the need for GNE function and enables protein sialylation. Studies in mutant mouse models demonstrated that oral ManNAc therapy improved pathologic features of both GNE Myopathy and glomerular diseases associated with hyposialylation. Clinical studies have demonstrated that twice-daily oral ManNAc supplementation led to significant and sustained increases in the circulating levels of sialic acid.
ManNAc is currently under investigation in collaboration with NHGRI and NCATS researchers (NIH) in an open-label Phase 2 study for the treatment of GNE Myopathy. The FDA has provided orphan designation for ManNAc in GNE Myopathy.
In addition, a Phase 1 study to investigate ManNAc safety and tolerability in patients with a range of glomerular diseases (primary podocyte diseases) associated with hyposialylation is currently recruiting.