Prominent therapeutic potential of peracetylated N‐acetylmannosamine, a synthetic sugar molecule, in DMRV/hIBM mice

We recently showed that muscle atrophy and weakness were completely prevented in the DMRV/hIBM mouse after treatment with natural sugar compounds (NeuAc, ManNAc, sialyllactose). Although this prophylactic treatment was effective, the increase of sialic acid was minimal in serum and modest in the skeletal muscles. To increase the serum and the bound sialic acid of tissues more remarkably, we screened several synthetic sugar compounds using primary DMRV/hIBM cultured cells and observed that cell sialylation was highest with tetra‐ O ‐acetylated ManNAc (Ac 4 ManNAc). To evaluate the efficacy of this compound in vivo, we administered Ac 4 ManNAc to DMRV/hIBM mice in two doses by oral route. Treatment of Ac 4 ManNAc dose‐dependently improved survival, led to amelioration of muscle weakness and atrophy in DMRV/hIBM mice, and prevented appearance of RVs and occurrence of amyloid. More importantly, sialylation in various tissues including skeletal muscle, was increased by Ac 4 ManNAc to a level higher than those when natural compounds were used. Furthermore, Ac 4 ManNAc treatment improved sialylation status of some glycoproteins in muscle, in a dose‐dependent manner. Our results support the use of Ac 4 ManNAc as a potential drug for therapy toward DMRV/hIBM.