Targeting GNE Myopathy: A Dual Prodrug Approach for the Delivery of -Acetylmannosamine 6-Phosphate.

ProTides comprise an important class of prodrugs currently marketed and developed as antiviral and anticancer therapies. The ProTide technology employs phosphate masking groups capable of providing more favorable druglike properties and an intracellular activation mechanism for enzyme-mediated release of a nucleoside monophosphate. Herein, we describe the application of phosphoramidate chemistry to 1,3,4--acetylated -acetylmannosamine (AcManNAc) to deliver ManNAc-6-phosphate (ManNAc-6-P), a critical intermediate in sialic acid biosynthesis.

Novel GNE mutations in autosomal recessive hereditary inclusion body myopathy patients.

Hereditary Inclusion Body Myopathy (HIBM, IBM2, MIM:600737) is an autosomal recessive adult onset progressive muscle wasting disorder. It is associated with the degeneration of distal and proximal muscles, while often sparing the quadriceps. The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK), encoded by the GNE gene, catalyzes the first two committed, rate-limiting steps in the biosynthesis of N-acetylneunaminic acid (sialic acid).