Update on Muscular Dystrophies with Focus on Novel Treatments and Biomarkers

Datta, Neil; Ghosh, Partha S.

doi:10.1007/s11910-020-01034-6

Cited by 24 publications

(33 citation statements)

References 102 publications

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“…This finding supports the potential use of serum TNNI-2 as a therapeutic biomarker that could measure treatment response of DMD patients receiving disease-modifying therapy. 9 However, while DMD, BMD, and healthy controls showed statistically significant differences for groups, there was overlap, and a TNNI-2 level of 10 ng/mL could place a subject in any of the three groups. Positive and negative predictive values and the receiver operating characteristic (ROC) curve, created by plotting the true positive rate against the false positive rate, were not provided by the authors.…”

mentioning

confidence: 88%

Biomarkers in Duchenne and Becker muscular dystrophies

McMillan

Lochmüller

2021

Muscle and Nerve

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Biomarkers are quantifiable markers of an underlying biological disease. Diagnostic biomarkers may facilitate early diagnosis, whereas therapeutic biomarkers may permit measurement of potential response to a disease-modifying therapy. 1 Biomarkers have been highly sought after in Duchenne (DMD) and Becker (BMD) muscular dystrophies, diseases characterized by the absence or reduction of normal dystrophin protein. Muscle fibers are fragile and susceptible to tearing. Although there is limited capacity for repair and regeneration, myonecrosis and replacement with connective tissue eventually occurs with disease progression.Older serum markers such as creatine kinase (CK) or lactate dehydrogenase lack specificity for skeletal muscle. Serum CK is markedly

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mentioning

confidence: 88%

Biomarkers in Duchenne and Becker muscular dystrophies

McMillan

Lochmüller

2021

Muscle and Nerve

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“…Of the many muscular dystrophies, DMD is not only the commonest, but the most severe (Datta and Ghosh 2020). Nevertheless, DMD fibers can survive 20-30 years, progressively more debilitated by chronic ischemia, plagued by sarcolemmal damage.…”

Section: Ion Homeostasis and Dmd Smfsmentioning

confidence: 99%

Donnan dominated ion homeostasis and the longevity of ischemic Na⁺-loaded dystrophic skeletal muscle

Ce¹,

Wheeler

Joós

2020

Preprint

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The inherited muscle-wasting disease, Duchenne muscular dystrophy (DMD), renders skeletal muscle fibers (SMFs) Na+-overloaded, ischemic, membrane-damaged, cation-leaky, depolarized, and prone to myogenic firing. DMD fibers nevertheless survive up to 3 decades before succumbing to Ca2+-necrosis. The Ca2+-necrosis is explicable, the longevity is not. Modeling here shows that SMFs’ ion homeostasis strategy, a low-cost resilient Pump-Leak/Donnan feedback process we term “Donnan dominated”, underpins that longevity. Together, SMFs’ huge chloride-permeability and tiny sodium-permeability minimize excitability and pump costs, facilitating the outsized SMF pump-reserve that lets DMD fibers withstand deep ischemia and leaky channels. We illustrate how, as these impairments intensify, patients’ chronic Na+-overload (now non-invasively evident via Na23-MRI) would change. In simulations, prolonged excitation (→physiological Na+-overloading) and/or intense ischemia (→too little Na+-pumping) and accumulated bleb-damage (→too much Na+-leaking) eventually trigger Ca2+-overloading conditions. Our analysis implies an urgent need to identify SMFs’ pivotal small PNa, thereby opening new therapeutic remediation routes.

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“…Although no treatment currently can prevent or reverse the effects of Duchenne muscular dystrophy (DMD), several pharmacologic, cellular, and genetic approaches may reduce disease effects and improve the quality of life for DMD patients. 1 In assessing the outcomes of clinical trials of these treatments, objective biomarkers must be developed and assessed longitudinally in natural history studies. 2 Ideally, these biomarkers should be compared against results from the histological analysis of muscle biopsies, which has historically been used as the gold standard for disease assessment.…”

Section: Introductionmentioning

confidence: 99%

Using MRI to quantify skeletal muscle pathology in Duchenne muscular dystrophy: A systematic mapping review

et al. 2021

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There is a great demand for accurate non-invasive measures to better define the natural history of disease progression or treatment outcome in Duchenne muscular dystrophy (DMD) and to facilitate the inclusion of a large range of participants in DMD clinical trials. This review aims to investigate which MRI sequences and analysis methods have been used and to identify future needs. Medline, Embase, Scopus, Web of Science, Inspec, and Compendex databases were searched up to 2 November 2019, using keywords "magnetic resonance imaging" and "Duchenne muscular dystrophy." The review showed the trend of using T1w and T2w MRI images for semi-qualitative inspection of structural alterations of DMD muscle using a diversity of grading scales, with increasing use of T2map, Dixon, and MR spectroscopy (MRS).High-field (>3T) MRI dominated the studies with animal models. The quantitative MRI techniques have allowed a more precise estimation of local or generalized disease severity. Longitudinal studies assessing the effect of an intervention have also become more prominent, in both clinical and animal model subjects. Quality assessment of the included longitudinal studies was performed using the Newcastle-Ottawa Quality Assessment Scale adapted to comprise bias in selection, comparability, exposure, and outcome. Additional large clinical trials are needed to consolidate research using MRI as a biomarker in DMD and to validate findings against established gold standards. This future work should use a multiparametric and quantitative MRI acquisition protocol, assess the repeatability of measurements, and correlate findings to histologic parameters.

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Update on Muscular Dystrophies with Focus on Novel Treatments and Biomarkers

Cited by 24 publications

References 102 publications

Biomarkers in Duchenne and Becker muscular dystrophies

Biomarkers in Duchenne and Becker muscular dystrophies

Donnan dominated ion homeostasis and the longevity of ischemic Na⁺-loaded dystrophic skeletal muscle

Using MRI to quantify skeletal muscle pathology in Duchenne muscular dystrophy: A systematic mapping review

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Update on Muscular Dystrophies with Focus on Novel Treatments and Biomarkers

Cited by 24 publications

References 102 publications

Biomarkers in Duchenne and Becker muscular dystrophies

Biomarkers in Duchenne and Becker muscular dystrophies

Donnan dominated ion homeostasis and the longevity of ischemic Na+-loaded dystrophic skeletal muscle

Using MRI to quantify skeletal muscle pathology in Duchenne muscular dystrophy: A systematic mapping review

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Donnan dominated ion homeostasis and the longevity of ischemic Na⁺-loaded dystrophic skeletal muscle