Multiplex Screen of Serum Biomarkers in Facioscapulohumeral Muscular Dystrophy

Statland, Jeffrey; Donlin-Smith, Colleen M.; Tapscott, Stephen J.; Maarel, Silvère M. van der; Tawil, Rabi

doi:10.3233/jnd-140034

Cited by 42 publications

(35 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, expression of ADAMTS5 was previously shown to be elevated in the muscle of FSHD patients 38 . Notably, potential serum protein biomarkers for FSHD were recently identified in an antibody-based screen, although ADAMTS5 was not included in the panel of antibodies tested 39 .…”

Section: Discussionmentioning

confidence: 99%

Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics

Coenen-Stass

McClorey

Manzano

et al. 2015

Sci Rep

View full text Add to dashboard Cite

There is currently an urgent need for biomarkers that can be used to monitor the efficacy of experimental therapies for Duchenne Muscular Dystrophy (DMD) in clinical trials. Identification of novel protein biomarkers has been limited due to the massive complexity of the serum proteome and the presence of a small number of very highly abundant proteins. Here we have utilised an aptamer-based proteomics approach to profile 1,129 proteins in the serum of wild-type and mdx (dystrophin deficient) mice. The serum levels of 96 proteins were found to be significantly altered (P < 0.001, q < 0.01) in mdx mice. Additionally, systemic treatment with a peptide-antisense oligonucleotide conjugate designed to induce Dmd exon skipping and recover dystrophin protein expression caused many of the differentially abundant serum proteins to be restored towards wild-type levels. Results for five leading candidate protein biomarkers (Pgam1, Tnni3, Camk2b, Cycs and Adamts5) were validated by ELISA in the mouse samples. Furthermore, ADAMTS5 was found to be significantly elevated in human DMD patient serum. This study has identified multiple novel, therapy-responsive protein biomarkers in the serum of the mdx mouse with potential utility in DMD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics

Coenen-Stass

McClorey

Manzano

et al. 2015

Sci Rep

View full text Add to dashboard Cite

show abstract

“…It seeks to open an avenue for biomarker discovery. Similar exploratory biomarker studies on this assay platform have been performed for diseases such as facioscapulohumeral muscular dystrophy (15) and chronic obstructive pulmonary disease (16). Within the 90 proteins surveyed, there was a subset of ILs and several other proteins that were lower than controls at baseline, and normalized with treatment: IL-1α, IL-7, IL-13, as well as beta-2 microglobulin, C-reactive protein, and myoglobin.…”

Section: Discussionmentioning

confidence: 77%

Survey of plasma proteins in children with progeria pre-therapy and on-therapy with lonafarnib

et al. 2018

View full text Add to dashboard Cite

BackgroundHutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare, fatal, segmental premature aging syndrome caused by the aberrant lamin A protein, progerin. The protein farnesyltransferase inhibitor, lonafarnib, ameliorates some aspects of cardiovascular and bone disease.MethodsWe performed a prospective longitudinal survey of plasma proteins in 24 children with HGPS (an estimated 10% of the world's population at the time) at baseline and on lonafarnib therapy, compared with age- and gender-matched controls using a multi-analyte, microsphere-based immunofluorescent assay.ResultsThe mean levels for 23/66 (34.8%) proteins were significantly lower and 7/66 (10.6%) were significantly higher in HGPS samples compared with those in controls (P≤0.05). Six proteins whose concentrations were initially lower normalized with lonafarnib therapy: interleukins 1α, 7, and 13, beta-2 microglobulin, C-reactive protein, and myoglobin. Alpha-2 macroglobulin, a protease inhibitor associated with stroke, was elevated at baseline and subsequently normalized with lonafarnib therapy.ConclusionThis is the first study to employ a multi-analyte array platform in HGPS. Novel potential biomarkers identified in this study should be further validated by correlations with clinical disease status, especially proteins associated with cardiovascular disease and those that normalized with lonafarnib therapy.

show abstract

“…However, an updated study shows that PAX7 target gene expression is a superior FSHD biomarker than the DUX4 target gene approach, associating with pathological severity. Besides, proteomics findings and the miRNA of patient sera are potential biomarker candidates to predict the disease state and correlate with disease severity in FSHD [ 59 , 60 ]. Nevertheless, long-term studies that monitor their levels beginning from a young age are still lacking, representing an authentic biomarker for infantile FSHD.…”

Section: Laboratory Findings and Potential Biomarkers Of Fshdmentioning

confidence: 99%

Early-Onset Infantile Facioscapulohumeral Muscular Dystrophy: A Timely Review

Chen

Tseng

2020

IJMS

View full text Add to dashboard Cite

Facioscapulohumeral muscular dystrophy (FSHD)—the worldwide third most common inherited muscular dystrophy caused by the heterozygous contraction of a 3.3 kb tandem repeat (D4Z4) on a chromosome with a 4q35 haplotype—is a progressive genetic myopathy with variable onset of symptoms, distribution of muscle weakness, and clinical severity. While much is known about the clinical course of adult FSHD, data on the early-onset infantile phenotype, especially on the progression of the disease, are relatively scarce. Contrary to the classical form, patients with infantile FSHD more often have a rapid decline in muscle wasting and systemic features with multiple extramuscular involvements. A rough correlation between the phenotypic severity of FSHD and the D4Z4 repeat size has been reported, and the majority of patients with infantile FSHD obtain a very short D4Z4 repeat length (one to three copies, EcoRI size 10–14 kb), in contrast to the classical, slowly progressive, form of FSHD (15–38 kb). With the increasing identifications of case reports and the advance in genetic diagnostics, recent studies have suggested that the infantile variant of FSHD is not a genetically separate entity but a part of the FSHD spectrum. Nevertheless, many questions about the clinical phenotype and natural history of infantile FSHD remain unanswered, limiting evidence-based clinical management. In this review, we summarize the updated research to gain insight into the clinical spectrum of infantile FSHD and raise views to improve recognition and understanding of its underlying pathomechanism, and further, to advance novel treatments and standard care methods.

show abstract

Multiplex Screen of Serum Biomarkers in Facioscapulohumeral Muscular Dystrophy

Cited by 42 publications

References 31 publications

Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics

Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics

Survey of plasma proteins in children with progeria pre-therapy and on-therapy with lonafarnib

Early-Onset Infantile Facioscapulohumeral Muscular Dystrophy: A Timely Review

Contact Info

Product

Resources

About