Comparative mass spectrometric and immunoassay‐based proteome analysis in serum of Duchenne muscular dystrophy patients

Abstract

The combined results of MS- and ELISA-based quantifications indicated more studies are needed to validate this serum protein signature for DMD patients. With these data promising candidate biomarkers have been identified for a rare genetic disease using serum proteome analysis.

Proteomic profiling of mdx-4cv serum reveals highly elevated levels of the inflammation-induced plasma marker haptoglobin in muscular dystrophy

“…Elevated levels of previously identified proteomic serum markers were also confirmed (Tables I and II), such as fibronectin, coagulation factor V, titin, myosin light chain 1/3, fructose-bisphosphate aldolase (isoforms A–C), phosphoglucomutase (isoforms 1 and 2), enolase (isoforms α, β and γ), glycogen phosphorylase (muscle and liver isoforms), fatty acid-binding protein (adipocyte, epidermal, liver and heart isoforms), cytochrome c , malate dehydrogenase (cytoplasmic and mitochondrial isoform), parvalbumin, troponin (muscle isoforms TnI and TnC) and various heat-shock proteins (HSP90-β, HSP90-α, HSP70, HSP β-1, HSP cognate 71) (30–39). These findings demonstrate the reproducibility of the findings from a large number of biochemical and proteomic surveys of serum and plasma preparations from dystrophic patients and animal models of Duchenne muscular dystrophy.…”

“…This primary mechanism of fibre damage is accompanied by adaptive responses, such as myofibrosis (10), and secondary changes related to an inflammatory pathology (16). In addition to massive proteome-wide changes within skeletal muscle fibres (46,50–52,60,72–74), the deficiency in dystrophin isoform Dp427 also causes substantial alterations in the rate of protein release from muscle tissues into the circulatory system and other plasma fluctuations (30–39). This includes actively secreted proteins and passively released components from mechanically damaged fibres and other types of tissue (29).…”

“…In the field of muscular dystrophy research, the systematic screening of body fluids from Duchenne patients and established animal models of dystrophinopathies using proteomic technology has recently established a variety of new biomarker candidates, including fibronectin, the coagulation factor XIIIa, titin, various myosin light chain isoforms, myomesin-3, filamin-C, lysosomal-associated membrane protein LAMP1 and its accompanying vesicle proteins, aldolase, phosphoglycerate mutase, enolase, glycogen phosphorylase, fatty acid-binding protein, myoglobin, cytochrome c , malate dehydrogenase, fibrinogen, parvalbumin, electron transfer flavoprotein A, troponin, Ca 2+ /calmodulin-dependent protein kinase Camk2b, metalloproteinase Adamts5, troponin-1, myoglobin and heat-shock protein HSPA1A (30–39). In analogy to these studies and to establish new biomarker candidates for the improved evaluation of animal models of dystrophinopathy, we analysed serum from the dystrophic mdx - 4cv mouse (40).…”

Tracking disease progression non‐invasively in Duchenne and Becker muscular dystrophies

“…The identification of biomarkers for DMD is a priority to the field to identify prognostic factors and to provide objective readouts to reliably evaluate patients' response to drugs in clinical trials . Several muscle specific molecular entities have been detected in biofluids such as serum, plasma, and urine showing that it is possible to obtain direct muscle‐related information without an invasive muscle biopsy . Muscle‐derived proteins such as muscle creatine kinase (CK) are known to be highly elevated in patients' blood in the early phases of the disease and to decrease over time as muscle mass is lost .…”

Cross‐sectional serum metabolomic study of multiple forms of muscular dystrophy

“…The identification of non‐invasive biomarkers able to monitor disease progression and response to therapy would enable better patients’ management and faster evaluation and marketing authorization of medicinal products for DMD and MDs in general. Towards this aim, multiple groups are working to identify biomarkers in body fluids such as blood‐derived samples and urine . Most of the available information was obtained by studying protein concentrations in different samples matrices and miRNAs, while less information is available for metabolites concentration in body fluids, even though DMD was considered in the past and recently re‐evaluated to be a metabolic myopathy .…”