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Identification of biomarkers for GNE myopathy
Author(s) -
Malicdan May Christine,
Momma Kazunari,
Nishino Ichizo,
Noguchi Satoru
Publication year - 2012
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.26.1_supplement.1122.3
Subject(s) - sialic acid , myopathy , amyloid (mycology) , albumin , phenotype , chemistry , biochemistry , microbiology and biotechnology , medicine , gene , pathology , endocrinology , biology
GNE‐myopathy is an autosomal recessive disorder characterized by muscle atrophy and weakness, and accumulation of amyloid proteins and rimmed vacuoles in myofibers. This disease is secondary to mutations in the GNE gene, which encodes an essential enzyme in sialic acid biosynthesis. Recently, we reported that the sialic acid treatment is effective to prevent myopathic phenotype in model mice. In translating these results to a clinical trial for GNE myopathy, there is a need for establishing indicators of disease state or therapeutic effects. In this study, we identified the molecular biomarkers in blood of GNE myopathic patients. We measured sialic acid content by HPLC and β amyloid content by ELISA, and examined proteomic change of albumin and IgG‐depleted plasma by differential 2D‐gel electrophoresis (DIGE). In sialic acid content in blood, average values of sialic acid contents in blood are 397 ± 27 nmol/ml and 861 ± 23 nmol/ml for patients (n=46) and controls (n=21), respectively (p<0.0001). In Amyloid measurement, the average values for Aβ1–40, Aβ1–42 are similar between patients (n=29) and control (n=8) (p=0.17 and p=0.82), however patients showed much variation in both amyloid contents, indicating blood amyloid levels raise in some patients. In proteomic analysis of patient specimens (n=6) and control (n=6), we identified several spots including serotransferrin, were shifted horizontally from acidic to basic side in patients, and some spots showed changes in expression. These results showed that the protein sialylation as well as the proteins showing difference in expression, including amyloid can be used as biomarkers for therapeutic trials.