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Lectin Staining Biomarkers for Gene Therapy in GNE Myopathy
Author(s) -
Crowe Kelly E.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.07098
Subject(s) - wasting , myopathy , genetic enhancement , sialic acid , gene , biology , disease , medicine , bioinformatics , microbiology and biotechnology , cancer research , biochemistry , genetics
GNE myopathy (GNEM) is an autosomal recessive disease characterized by muscle wasting and weakness. This disease is caused by mutations in the GNE (UDP‐N‐acetylglucosamine (GlcNAc) 2‐epimerase/N‐acetylmannosamine (ManNAc) kinase) gene, which encodes a bifunctional enzyme that catalyzes the committed step of sialic acid (SA) biosynthesis. As such, GNE mutations found in GNEM impair enzymatic function and generally result in a decrease of SA. Efforts to treat GNEM with gene therapy are currently underway, but given the slowly progressing muscle pathology of GNEM, it becomes important to establish molecular biomarkers to assess such a therapy during the relatively brief timescale of a clinical trial. To do so, we have compared SA abundance in converted myoblasts from GNEM and otherwise normal patients using fluorescently labeled lectins, which can reflect cellular SA levels. Here, we describe changes in SA abundance in GNE myopathy that could serve as surrogate biomarkers for a GNE gene therapy clinical trial. Support or Funding Information This work was supported by a grant from the Neuromuscular Disease Foundation (NDF).