226th ENMC International Workshop:

Aartsma‐Rus, Annemieke; Ferlini, Alessandra; McNally, Elizabeth M.; Spitali, Pietro; Hl, Sweeney

doi:10.1016/j.nmd.2017.10.002

Cited by 11 publications

(2 citation statements)

References 39 publications

(36 reference statements)

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“…Biomarkers are an unmet need also in DMD clinical trials either for monitoring available therapies or developing new ones, also considering that currently used standardised outcome measures include physical and imaging tests, which are either slow in delivering results or low throughput and costly [ 17 ]. The DYS protein assay in muscle biopsy is the only European Medicines Agency (EMA)-approved pharmacodynamic biomarker to monitor DMD-restoring therapies [ 18 ]. Dystrophin is normally expressed at low, and not constant, levels among individuals [ 19 ] and shows a lower rate of expression in DMD patients, making its detection extremely challenging [ 20 ], especially in fluids dominated by a high abundance of other proteins.…”

Section: Introductionmentioning

confidence: 99%

A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring

Rossi

Johansson

Heywood³

et al. 2023

IJMS

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Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity. To fill this critical gap, we present here novel data about dystrophin protein fragments detected in human plasma by a suspension bead immunoassay using two validated anti-dystrophin-specific antibodies. Using both antibodies, a reduction of the dystrophin signal is detected in a small cohort of plasma samples from DMD patients when compared to healthy controls, female carriers, and other neuromuscular diseases. We also demonstrate the detection of dystrophin protein by an antibody-independent method using targeted liquid chromatography mass spectrometry. This last assay detects three different dystrophin peptides in all healthy individuals analysed and supports our finding that dystrophin protein is detectable in plasma. The results of our proof-of-concept study encourage further studies in larger sample cohorts to investigate the value of dystrophin protein as a low invasive blood biomarker for diagnostic screening and clinical monitoring of DMD.

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Section: Introductionmentioning

confidence: 99%

A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring

Rossi

Johansson

Heywood³

et al. 2023

IJMS

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“…A biomarker should be quantifiable, reproducibly measurable with small coefficients of variation, and, whenever applied in the therapeutic field, it should predict the treatment response in a shorter timeframe than existing outcome measures. Evaluations of progressive disorder through measurable non-invasive biomarkers will provide clinicians with an invaluable tool for the care of patients affected by neuromuscular diseases (NMDs) [1]. In general, a biomarker, or biological marker, is a measurable indicator of some biological state or condition.…”

Section: Introductionmentioning

confidence: 99%

Circulating Biomarkers in Neuromuscular Disorders: What Is Known, What Is New

Barp¹,

Ferrero²,

Casagrande

et al. 2021

Biomolecules

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The urgent need for new therapies for some devastating neuromuscular diseases (NMDs), such as Duchenne muscular dystrophy or amyotrophic lateral sclerosis, has led to an intense search for new potential biomarkers. Biomarkers can be classified based on their clinical value into different categories: diagnostic biomarkers confirm the presence of a specific disease, prognostic biomarkers provide information about disease course, and therapeutic biomarkers are designed to predict or measure treatment response. Circulating biomarkers, as opposed to instrumental/invasive ones (e.g., muscle MRI or nerve ultrasound, muscle or nerve biopsy), are generally easier to access and less “time-consuming”. In addition to well-known creatine kinase, other promising molecules seem to be candidate biomarkers to improve the diagnosis, prognosis and prediction of therapeutic response, such as antibodies, neurofilaments, and microRNAs. However, there are some criticalities that can complicate their application: variability during the day, stability, and reliable performance metrics (e.g., accuracy, precision and reproducibility) across laboratories. In the present review, we discuss the application of biochemical biomarkers (both validated and emerging) in the most common NMDs with a focus on their diagnostic, prognostic/predictive and therapeutic application, and finally, we address the critical issues in the introduction of new biomarkers.

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