Recent developments in Duchenne muscular dystrophy: facts and numbers

BackgroundThis study was performed to test the therapeutic potential of obestatin, an autocrine anabolic factor regulating skeletal muscle repair, to ameliorate the Duchenne muscular dystrophy (DMD) phenotype.Methods and resultsUsing a multidisciplinary approach, we characterized the ageing‐related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4‐, 8‐, and 18‐week‐old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8‐week‐old mdx mice (n = 5/group). The findings were extended to in vitro effects on human immortalized DMD myotubes. An analysis of TAs revealed an age‐related loss of preproghrelin expression, as precursor of obestatin, in mdx mice. Administration of obestatin resulted in a significant increase in tetanic specific force (33.0% ± 1.5%, P < 0.05), compared with control mdx mice. Obestatin‐treated TAs were characterized by reduction of fibres with centrally located nuclei (10.0% ± 1.2%, P < 0.05) together with an increase in the number of type I fibres (25.2% ± 1.7%, P < 0.05) associated to histone deacetylases/myocyte enhancer factor‐2 and peroxisome proliferator‐activated receptor‐gamma coactivator 1α axis, and down‐regulation of ubiquitin E3‐ligases by inactivation of FoxO1/4, indexes of muscle atrophy. Obestatin reduced the level of contractile damage and tissue fibrosis. These observations correlated with decline in serum creatine kinase (58.8 ± 15.2, P < 0.05). Obestatin led to stabilization of the sarcolemma by up‐regulation of utrophin, α‐syntrophin, β‐dystroglycan, and α7β1‐integrin proteins. These pathways were also operative in human DMD myotubes.ConclusionsThese results highlight the potential of obestatin as a peptide therapeutic for preserving muscle integrity in DMD, thus allowing a better efficiency of gene or cell therapy in a combined therapeutic approach.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment

González‐Sánchez

Sánchez‐Temprano

Cid‐Díaz

et al. 2018

“…More recently, a number of publications have also covered the intriguing area of neuromuscular disorders, and Professor Jens Schmidt has joined the editorial team with an excellent knowledge of the area. [1][2][3][4][5][6][7][8] Special research interests otherwise include lipolysis, muscle wasting, and biomarkers for metabolic changes. The Journal is therefore attractive for many different medical specialities such as clinicians, physicians, trialists, basic scientists, pharmacologists, nurses, physiotherapists, biochemists, biologists, dieticians, and students.…”

mentioning

confidence: 99%

The Journal of Cachexia, Sarcopenia and Muscle stays the front‐runner in geriatrics and gerontology

Anker

Coats

et al. 2019

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. also looked at the top cited scientific papers ever published in the three journals (Tables 10-12) and found that on average, the top 10 papers in JCSM were cited 152 times, in Nutrition 670 times, and in JNHA 406 times-which is mainly due to the fact that Nutrition has been listed in Scopus 265 since 1987 and JNHA since 1997, while JCSM started only in 2010. So far, JCSM has published 563 papers, Nutrition 6198 papers, and JNHA 2396 papers. On average, JCSM has published 56 papers/year, Nutrition 188 papers/year, and JNHA 104 papers/year, which of course are major determinants of the respective journal's impact factor. This also underscores that all three journals have different approaches towards the number of papers published per year. We are grateful and look forward to more submissions of excellent research in the field of wasting and muscle disorders and are confident to maintain high quality in the Journal.

AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy

Abou‐Samra

Selvais

Boursereau

et al. 2020

Background Adiponectin (ApN) is a hormone known to exhibit insulin-sensitizing, fat-burning, and anti-inflammatory properties in several tissues, including the skeletal muscle. Duchenne muscular dystrophy (DMD) is a devastating disease characterized by dystrophin deficiency with subsequent chronic inflammation, myofiber necrosis, and impaired regeneration. Previously, we showed that transgenic up-regulation of ApN could significantly attenuate the dystrophic phenotype in mdx mice (model of DMD). Recently, an orally active ApN receptor agonist, AdipoRon, has been identified. This synthetic small molecule has the advantage of being more easily produced and administrable than ApN. The aim of this study was to investigate the potential effects of AdipoRon on the dystrophic muscle. Methods Four-week-old mdx mice (n = 6-9 per group) were orally treated with AdipoRon (mdx-AR) for 8 weeks and compared with untreated (mdx) mice and to control (wild-type) mice. In vivo functional tests were carried out to measure the global force and endurance of mice. Ex vivo biochemical and molecular analyses were performed to evaluate the pathophysiology of the skeletal muscle. Finally, in vitro tests were conducted on primary cultures of healthy and DMD human myotubes. Results AdipoRon treatment mitigated oxidative stress (À30% to 45% for 4-hydroxy-2-nonenal and peroxiredoxin 3, P < 0.0001) as well as inflammation in muscles of mdx mice (À35% to 65% for interleukin 1 beta, tumour necrosis factor alpha, and cluster of differentiation 68, a macrophage maker, P < 0.0001) while increasing the anti-inflammatory cytokine, interleukin 10 (~5-fold, P < 0.0001). AdipoRon also improved the myogenic programme as assessed by a~2-fold rise in markers of muscle proliferation and differentiation (P < 0.01 or less vs. untreated mdx). Plasma lactate dehydrogenase and creatine kinase were reduced by 30-40% in mdx-AR mice, reflecting less sarcolemmal damage (P < 0.0001). When compared with untreated mdx mice, mdx-AR mice exhibited enhanced physical performance with an increase in both muscle force and endurance and a striking restoration of the running capacity during eccentric exercise. AdipoRon mainly acted through ApN receptor 1 by increasing AMP-activated protein kinase signalling, which led to repression of nuclear factor-kappa B, upregulation of utrophin (a dystrophin analogue), and a switch towards an oxidative and more resistant fibre phenotype. The effects of AdipoRon were then recapitulated in human DMD myotubes. Conclusions These results demonstrate that AdipoRon exerts several beneficial effects on the dystrophic muscle. This molecule could offer promising therapeutic prospect for managing DMD or other muscle and inflammatory disorders.