A Nitrate Ester of Sedative Alkyl Alcohol Improves Muscle Function and Structure in a Murine Model of Duchenne Muscular Dystrophy

2013 ◽  
Vol 10 (10) ◽  
pp. 3862-3870 ◽  
Author(s):  
Guqi Wang ◽  
Qilong Lu
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Murine Model ◽  
Muscle Function ◽  
Nitrate Ester

scholarly journals Metformin Increases Sarcolemma Integrity and Ameliorates Neuromuscular Deficits in a Murine Model of Duchenne Muscular Dystrophy

2021 ◽  
Vol 12 ◽  
Author(s):  
Xia Dong ◽  
Tiankun Hui ◽  
Jie Chen ◽  
Zheng Yu ◽  
Dongyan Ren ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Murine Model ◽  
Muscle Function ◽  
Membrane Integrity ◽  
Therapeutic Drug ◽  
Mdx Mice ◽  
Protein Levels ◽  
Progressive Muscle Weakness ◽  
Electron Microscopy Analysis

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disease characterized by progressive muscle weakness and wasting. Stimulation of AMP-activated protein kinase (AMPK) has been demonstrated to increase muscle function and protect muscle against damage in dystrophic mice. Metformin is a widely used anti-hyperglycemic drug and has been shown to be an indirect activator of AMPK. Based on these findings, we sought to determine the effects of metformin on neuromuscular deficits in mdx murine model of DMD. In this study, we found metformin treatment increased muscle strength accompanied by elevated twitch and tetanic force of tibialis anterior (TA) muscle in mdx mice. Immunofluorescence and electron microscopy analysis of metformin-treated mdx muscles revealed an improvement in muscle fiber membrane integrity. Electrophysiological studies showed the amplitude of miniature endplate potentials (mEPP) was increased in treated mice, indicating metformin also improved neuromuscular transmission of the mdx mice. Analysis of mRNA and protein levels from muscles of treated mice showed an upregulation of AMPK phosphorylation and dystrophin-glycoprotein complex protein expression. In conclusion, metformin can indeed improve muscle function and diminish neuromuscular deficits in mdx mice, suggesting its potential use as a therapeutic drug in DMD patients.

Beneficial role of adipose‐derived mesenchymal stem cells from microfragmented fat in a murine model of duchenne muscular dystrophy

2019 ◽  
Vol 60 (3) ◽  
pp. 328-335 ◽  
Author(s):  
Adrien Bouglé ◽  
Pierre Rocheteau ◽  
David Briand ◽  
David Hardy ◽  
Franck Verdonk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Murine Model ◽  
Beneficial Role

Muscle function and age are associated with loss of bone mineral density in Duchenne muscular dystrophy

2019 ◽  
Vol 59 (4) ◽  
pp. 417-421 ◽  
Author(s):  
Oriana Del Rocío Cruz-Guzmán ◽  
Maricela Rodríguez-Cruz ◽  
Tomas Almeida-Becerril ◽  
Jorge Maldonado-Hernández ◽  
Carlos Wong Baeza
Keyword(s):  
Bone Mineral Density ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Bone Mineral ◽  
Muscle Function ◽  
Mineral Density

scholarly journals Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function

Neurology ◽  
2019 ◽  
Vol 93 (13) ◽  
pp. e1312-e1323 ◽  
Author(s):  
Eric P. Hoffman ◽  
Benjamin D. Schwartz ◽  
Laurel J. Mengle-Gaw ◽  
Edward C. Smith ◽  
Diana Castro ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Natural History ◽  
Muscle Function ◽  
Open Label ◽  
Suspension Formulation ◽  
Efficacy Outcome ◽  
Dose Study ◽  
Dose Levels

ObjectiveTo study vamorolone, a first-in-class steroidal anti-inflammatory drug, in Duchenne muscular dystrophy (DMD).MethodsAn open-label, multiple-ascending-dose study of vamorolone was conducted in 48 boys with DMD (age 4–<7 years, steroid-naive). Dose levels were 0.25, 0.75, 2.0, and 6.0 mg/kg/d in an oral suspension formulation (12 boys per dose level; one-third to 10 times the glucocorticoid dose in DMD). The primary goal was to define optimal doses of vamorolone. The primary outcome for clinical efficacy was time to stand from supine velocity.ResultsOral administration of vamorolone at all doses tested was safe and well tolerated over the 24-week treatment period. The 2.0–mg/kg/d dose group met the primary efficacy outcome of improved muscle function (time to stand; 24 weeks of vamorolone treatment vs natural history controls), without evidence of most adverse effects of glucocorticoids. A biomarker of bone formation, osteocalcin, increased in vamorolone-treated boys, suggesting possible loss of bone morbidities seen with glucocorticoids. Biomarker outcomes for adrenal suppression and insulin resistance were also lower in vamorolone-treated patients with DMD relative to published studies of glucocorticoid therapy.ConclusionsDaily vamorolone treatment suggested efficacy at doses of 2.0 and 6.0 mg/kg/d in an exploratory 24-week open-label study.Classification of evidenceThis study provides Class IV evidence that for boys with DMD, vamorolone demonstrated possible efficacy compared to a natural history cohort of glucocorticoid-naive patients and appeared to be tolerated.

scholarly journals Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1119
Author(s):  
Aleksandra Klimczak ◽  
Agnieszka Zimna ◽  
Agnieszka Malcher ◽  
Urszula Kozlowska ◽  
Katarzyna Futoma ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Bone Marrow ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Progenitor Cells ◽  
Muscle Function ◽  
Progenitor Cell ◽  
Genetic Disorder ◽  
Cell Populations ◽  
Muscle Fibres

Duchenne muscular dystrophy (DMD) is a genetic disorder associated with a progressive deficiency of dystrophin that leads to skeletal muscle degeneration. In this study, we tested the hypothesis that a co-transplantation of two stem/progenitor cell populations, namely bone marrow-derived mesenchymal stem cells (BM-MSCs) and skeletal muscle-derived stem/progenitor cells (SM-SPCs), directly into the dystrophic muscle can improve the skeletal muscle function of DMD patients. Three patients diagnosed with DMD, confirmed by the dystrophin gene mutation, were enrolled into a study approved by the local Bioethics Committee (no. 79/2015). Stem/progenitor cells collected from bone marrow and skeletal muscles of related healthy donors, based on HLA matched antigens, were expanded in a closed MC3 cell culture system. A simultaneous co-transplantation of BM-MSCs and SM-SPCs was performed directly into the biceps brachii (two patients) and gastrocnemius (one patient). During a six-month follow-up, the patients were examined with electromyography (EMG) and monitored for blood kinase creatine level. Muscle biopsies were examined with histology and assessed for dystrophin at the mRNA and protein level. A panel of 27 cytokines was analysed with multiplex ELISA. We did not observe any adverse effects after the intramuscular administration of cells. The efficacy of BM-MSC and SM-SPC application was confirmed through an EMG assessment by an increase in motor unit parameters, especially in terms of duration, amplitude range, area, and size index. The beneficial effect of cellular therapy was confirmed by a decrease in creatine kinase levels and a normalised profile of pro-inflammatory cytokines. BM-MSCs may support the pro-regenerative potential of SM-SPCs thanks to their trophic, paracrine, and immunomodulatory activity. Both applied cell populations may fuse with degenerating skeletal muscle fibres in situ, facilitating skeletal muscle recovery. However, further studies are required to optimise the dose and timing of stem/progenitor cell delivery.

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