O.10 Effect of combined treatment with soluble activin receptor IIB and AAV-U7-mediated dystrophin exon skipping on muscle function in mdx mice

2011 ◽  
Vol 21 (9-10) ◽  
pp. 703
Author(s):  
W.M.H. Hoogaars ◽  
E. Mouisel ◽  
K. Relizani ◽  
A. Pasternack ◽  
C. Hourde ◽  
...  
Keyword(s):  
Muscle Function ◽  
Combined Treatment ◽  
Exon Skipping ◽  
Mdx Mice ◽  
Activin Receptor ◽  
Activin Receptor Iib ◽  
O 10

scholarly journals Effects of Chronic, Maximal Phosphorodiamidate Morpholino Oligomer (PMO) Dosing on Muscle Function and Dystrophin Restoration in a Mouse Model of Duchenne Muscular Dystrophy

2021 ◽  
pp. 1-13
Author(s):  
Margaret E. Benny Klimek ◽  
Maria Candida Vila ◽  
Katie Edwards ◽  
Jessica Boehler ◽  
James Novak ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Function ◽  
Imaging Techniques ◽  
Exon Skipping ◽  
Becker Muscular Dystrophy ◽  
Mdx Mice ◽  
High Dose ◽  
Combination Treatments ◽  
Dystrophin Expression

Background: Phosphorodiamidate morpholino oligomer (PMO)-mediated exon skipping is currently used in clinical development to treat Duchenne muscular dystrophy (DMD), with four exon-skipping drugs achieving regulatory approval. Exon skipping elicits a truncated, but semi-functional dystrophin protein, similar to the truncated dystrophin expressed in patients with Becker Muscular dystrophy (BMD) where the disease phenotype is less severe than DMD. Despite promising results in both dystrophic animal models and DMD boys, restoration of dystrophin by exon skipping is highly variable, leading to contradictory functional outcomes in clinical trials. Objective: To develop optimal PMO dosing protocols that result in increased dystrophin and improved outcome measures in preclinical models of DMD. Methods: Tested effectiveness of multiple chronic, high dose PMO regimens using biochemical, histological, molecular, and imaging techniques in mdx mice. Results: A chronic, monthly regimen of high dose PMO increased dystrophin rescue in mdx mice and improved specific force in the extensor digitorum longus (EDL) muscle. However, monthly high dose PMO administration still results in variable dystrophin expression localized throughout various muscles. Conclusions: High dose monthly PMO administration restores dystrophin expression and increases muscle force; however, the variability of dystrophin expression at both the inter-and intramuscular level remains. Additional strategies to optimize PMO uptake including increased dosing frequencies or combination treatments with other yet-to-be-defined therapies may be necessary to achieve uniform dystrophin restoration and increases in muscle function.

scholarly journals Voluntary wheel running complements microdystrophin gene therapy to improve muscle function in mdx mice

2021 ◽  
Author(s):  
S.E. Hamm ◽  
D.D. Fathalikhani ◽  
K.E. Bukovec ◽  
A.K. Addington ◽  
H. Zhang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Muscle Function ◽  
Wheel Running ◽  
Mdx Mice ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

A fusion peptide directs enhanced systemic dystrophin exon skipping and functional restoration in dystrophin-deficient mdx mice

2018 ◽  
Vol 28 (4) ◽  
pp. 699-699 ◽  
Author(s):  
HaiFang Yin ◽  
Hong M Moulton ◽  
Corinne Betts ◽  
Yiqi Seow ◽  
Jordan Boutilier ◽  
...  
Keyword(s):  
Exon Skipping ◽  
Fusion Peptide ◽  
Functional Restoration ◽  
Mdx Mice

scholarly journals Celecoxib treatment improves muscle function in mdx mice and increases utrophin A expression

2018 ◽  
Vol 32 (9) ◽  
pp. 5090-5103 ◽  
Author(s):  
Christine Péladeau ◽  
Nadine J. Adam ◽  
Bernard J. Jasmin
Keyword(s):  
Muscle Function ◽  
Mdx Mice

scholarly journals A Case Report of a Patient with Guillain-Barre Syndrome Who Complained of Quadriplegia

2021 ◽  
Vol 42 (5) ◽  
pp. 1009-1019
Author(s):  
Gi-yoon Heo ◽  
Chan Lee ◽  
Im-hak Cho ◽  
Hee-kyung Kang ◽  
Min-hwa Kim ◽  
...  
Keyword(s):  
Muscle Weakness ◽  
Muscle Function ◽  
Hospital Admissions ◽  
Combined Treatment ◽  
Gait Pattern ◽  
Guillain Barre Syndrome ◽  
Poor Prognostic Factor ◽  
Guillain Barré Syndrome ◽  
Guillain Barré

Purpose: The aim of this study was to report the improvement of Guillain-Barre syndrome after long-term combination treatment with Korean medicine.Methods: A patient was diagnosed with Guillain-Barre syndrome and treated with herbal medicine, acupuncture, pharmacopuncture, moxibustion, and exercise, including quadruped walking after three hospital admissions. To evaluate muscle strength and weakness, we measured manual muscle function, gait pattern, and the speed of quadruped walking.Results: The patient's muscle weakness in the extremities and gait stance were improved. The speed of quadruped walking was increased.Conclusion: We consider that combined treatment with Korean medicine might be effective for the muscle weakness of Guillain-Barre syndrome with a poor prognostic factor. To verify the effectiveness of this treatment, further research is needed.

scholarly journals Molecular characteristic of activin receptor IIB and its functions in growth and nutrient regulation in Eriocheir sinensis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9673
Author(s):  
Jingan Wang ◽  
Kaijun Zhang ◽  
Xin Hou ◽  
Wucheng Yue ◽  
He Yang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Eriocheir Sinensis ◽  
Negative Regulator ◽  
Control Group ◽  
Molting Cycle ◽  
Activin Receptor ◽  
Activin Receptor Iib

Activin receptor IIB (ActRIIB) is a serine/threonine-kinase receptor binding with transforming growth factor-β (TGF-β) superfamily ligands to participate in the regulation of muscle mass in vertebrates. However, its structure and function in crustaceans remain unknown. In this study, the ActRIIB gene in Eriocheir sinensis (Es-ActRIIB) was cloned and obtained with a 1,683 bp open reading frame, which contains the characteristic domains of TGF-β type II receptor superfamily, encoding 560 amino acids. The mRNA expression of Es-ActRIIB was the highest in hepatopancreas and the lowest in muscle at each molting stage. After injection of Es-ActRIIB double-stranded RNA during one molting cycle, the RNA interference (RNAi) group showed higher weight gain rate, higher specific growth rate, and lower hepatopancreas index compared with the control group. Meanwhile, the RNAi group displayed a significantly increased content of hydrolytic amino acid in both hepatopancreas and muscle. The RNAi group also displayed slightly higher contents of saturated fatty acid and monounsaturated fatty acid but significantly decreased levels of polyunsaturated fatty acid compared with the control group. After RNAi on Es-ActRIIB, the mRNA expressions of five ActRIIB signaling pathway genes showed that ActRI and forkhead box O (FoxO) were downregulated in hepatopancreas and muscle, but no significant expression differences were found in small mother against decapentaplegic (SMAD) 3, SMAD4 and mammalian target of rapamycin. The mRNA expression s of three lipid metabolism-related genes (carnitine palmitoyltransferase 1β (CPT1β), fatty acid synthase, and fatty acid elongation) were significantly downregulated in both hepatopancreas and muscle with the exception of CPT1β in muscles. These results indicate that ActRIIB is a functionally conservative negative regulator in growth mass, and protein and lipid metabolism could be affected by inhibiting ActRIIB signaling in crustacean.

scholarly journals Blockade of the Activin Receptor IIB Activates Functional Brown Adipogenesis and Thermogenesis by Inducing Mitochondrial Oxidative Metabolism

2012 ◽  
Vol 32 (14) ◽  
pp. 2871-2879 ◽  
Author(s):  
B. Fournier ◽  
B. Murray ◽  
S. Gutzwiller ◽  
S. Marcaletti ◽  
D. Marcellin ◽  
...  
Keyword(s):  
Oxidative Metabolism ◽  
Activin Receptor ◽  
Activin Receptor Iib ◽  
Mitochondrial Oxidative Metabolism ◽  
Brown Adipogenesis
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