ProDGNE: Novel therapeutic approaches to target GNE Myopathy

GNE myopathy (GNEM) is a rare severely debilitating muscle disease which affects 1 to 9:1,000,000 people among all ethnicities, with elevated carrier rates in populations of Eastern Europe and Asian heritage, including Jewish, Persian, East Indian, Arab and Japanese. GNEM is characterized by hypo-sialylation of muscle glycoproteins, atrophy and weakness of skeletal muscles, causing severe impairment of function and quality of life. It is caused by mutations in the GNE gene which encodes biosynthesis of the sialic acid enzyme. There are no approved therapies and research efforts on sialylation-increasing therapies such as Neu5Ac and ManNAc are challenged by drug absorption and the absence of biomarkers in clinical development which are the main focus of our project. ProDGNE aims to overcome these obstacles through a joint collaboration among European and Canadian experts in clinical GNEM and basic research in sialic acid, organic synthesis, and -OMICS. Our developed prodrug when processed within cells becomes an active therapy, highly increasing sialic acid in GNEM patient cells and demonstrating a higher stability when compared to clinically tested drugs. The ProDGNE consortium will develop proof of principle studies fostering early stage development for innovative therapeutic strategies tested in vitro in patient derived cells and in vivo in GNE animal models that mimic the pathological mechanism in patients. Moreover, post-translational modifications will be explored and the newly identified biomarkers, will be utilized to monitor efficacy.