Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD). / Harish, Pradeep; Malerba, Alberto; Lu-Nguyen, Ngoc; Forrest, Leysa; Cappellari, Ornella; Roth, Fanny; Trollet, Capucine; Popplewell, Linda; Dickson, George.

In: Journal of Cachexia, Sarcopenia and Muscle, Vol. 10, No. 5, 10.2019, p. 1016-1026.

Research output: Contribution to journalArticlepeer-review

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Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD). / Harish, Pradeep; Malerba, Alberto; Lu-Nguyen, Ngoc; Forrest, Leysa; Cappellari, Ornella; Roth, Fanny; Trollet, Capucine; Popplewell, Linda; Dickson, George.

In: Journal of Cachexia, Sarcopenia and Muscle, Vol. 10, No. 5, 10.2019, p. 1016-1026.

Research output: Contribution to journalArticlepeer-review

Harvard

Harish, P, Malerba, A, Lu-Nguyen, N, Forrest, L, Cappellari, O, Roth, F, Trollet, C, Popplewell, L & Dickson, G 2019, 'Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD)', Journal of Cachexia, Sarcopenia and Muscle, vol. 10, no. 5, pp. 1016-1026. https://doi.org/10.1002/jcsm.12438

APA

Vancouver

Harish P, Malerba A, Lu-Nguyen N, Forrest L, Cappellari O, Roth F et al. Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD). Journal of Cachexia, Sarcopenia and Muscle. 2019 Oct;10(5):1016-1026. https://doi.org/10.1002/jcsm.12438

Author

Harish, Pradeep ; Malerba, Alberto ; Lu-Nguyen, Ngoc ; Forrest, Leysa ; Cappellari, Ornella ; Roth, Fanny ; Trollet, Capucine ; Popplewell, Linda ; Dickson, George. / Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD). In: Journal of Cachexia, Sarcopenia and Muscle. 2019 ; Vol. 10, No. 5. pp. 1016-1026.

BibTeX

@article{183606a528264277aba4179c8d16101b,
title = "Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD)",
abstract = "Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease affecting 1 per 80,000 of the general population characterised by profound dysphagia and ptosis, and limb weakness at later stages. Affected muscles are characterised by increased fibrosis and atrophy. Myostatin is a negative regulator of muscle mass, and inhibition of myostatin has been demonstrated to ameliorate symptoms in dystrophic muscles. Methods: In this study, we performed a systemic delivery of a monoclonal antibody to immunologically block myostatin in the A17 mouse model of OPMD. The mice were administered a weekly dose of 10mg/kg RK35 intraperitonially for 10 weeks, following which histological analyses were performed on the samples. Results: This treatment significantly (p<0.01) improved body mass (11%) and muscle mass (for the TA and EDL by 19% and 41%) in the A17 mice treated with RK35 when compared to saline controls. Similarly, a significantly (p<0.01) increased muscle strength (18% increase in maximal tetanic force) and myofibre diameter (17% and 44% for the TA and EDL) and reduced expression of markers of muscle fibrosis (40% reduction in area of expression), was also observed. No change in the density of intranuclear inclusions (a hallmark of disease progression of OPMD) was however observed.Conclusions: Our study supports the clinical translation of such antibody-mediated inhibition of myostatin as a treatment of OPMD. This strategy has implications to be used as adjuvant therapies with gene therapy based approaches, or to stabilise the muscle prior to myoblast transplantation.",
author = "Pradeep Harish and Alberto Malerba and Ngoc Lu-Nguyen and Leysa Forrest and Ornella Cappellari and Fanny Roth and Capucine Trollet and Linda Popplewell and George Dickson",
year = "2019",
month = oct,
doi = "10.1002/jcsm.12438",
language = "English",
volume = "10",
pages = "1016--1026",
journal = "Journal of Cachexia, Sarcopenia and Muscle",
issn = "2190-6009",
publisher = "Wiley",
number = "5",

}

RIS

TY - JOUR

T1 - Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD)

AU - Harish, Pradeep

AU - Malerba, Alberto

AU - Lu-Nguyen, Ngoc

AU - Forrest, Leysa

AU - Cappellari, Ornella

AU - Roth, Fanny

AU - Trollet, Capucine

AU - Popplewell, Linda

AU - Dickson, George

PY - 2019/10

Y1 - 2019/10

N2 - Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease affecting 1 per 80,000 of the general population characterised by profound dysphagia and ptosis, and limb weakness at later stages. Affected muscles are characterised by increased fibrosis and atrophy. Myostatin is a negative regulator of muscle mass, and inhibition of myostatin has been demonstrated to ameliorate symptoms in dystrophic muscles. Methods: In this study, we performed a systemic delivery of a monoclonal antibody to immunologically block myostatin in the A17 mouse model of OPMD. The mice were administered a weekly dose of 10mg/kg RK35 intraperitonially for 10 weeks, following which histological analyses were performed on the samples. Results: This treatment significantly (p<0.01) improved body mass (11%) and muscle mass (for the TA and EDL by 19% and 41%) in the A17 mice treated with RK35 when compared to saline controls. Similarly, a significantly (p<0.01) increased muscle strength (18% increase in maximal tetanic force) and myofibre diameter (17% and 44% for the TA and EDL) and reduced expression of markers of muscle fibrosis (40% reduction in area of expression), was also observed. No change in the density of intranuclear inclusions (a hallmark of disease progression of OPMD) was however observed.Conclusions: Our study supports the clinical translation of such antibody-mediated inhibition of myostatin as a treatment of OPMD. This strategy has implications to be used as adjuvant therapies with gene therapy based approaches, or to stabilise the muscle prior to myoblast transplantation.

AB - Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease affecting 1 per 80,000 of the general population characterised by profound dysphagia and ptosis, and limb weakness at later stages. Affected muscles are characterised by increased fibrosis and atrophy. Myostatin is a negative regulator of muscle mass, and inhibition of myostatin has been demonstrated to ameliorate symptoms in dystrophic muscles. Methods: In this study, we performed a systemic delivery of a monoclonal antibody to immunologically block myostatin in the A17 mouse model of OPMD. The mice were administered a weekly dose of 10mg/kg RK35 intraperitonially for 10 weeks, following which histological analyses were performed on the samples. Results: This treatment significantly (p<0.01) improved body mass (11%) and muscle mass (for the TA and EDL by 19% and 41%) in the A17 mice treated with RK35 when compared to saline controls. Similarly, a significantly (p<0.01) increased muscle strength (18% increase in maximal tetanic force) and myofibre diameter (17% and 44% for the TA and EDL) and reduced expression of markers of muscle fibrosis (40% reduction in area of expression), was also observed. No change in the density of intranuclear inclusions (a hallmark of disease progression of OPMD) was however observed.Conclusions: Our study supports the clinical translation of such antibody-mediated inhibition of myostatin as a treatment of OPMD. This strategy has implications to be used as adjuvant therapies with gene therapy based approaches, or to stabilise the muscle prior to myoblast transplantation.

U2 - 10.1002/jcsm.12438

DO - 10.1002/jcsm.12438

M3 - Article

VL - 10

SP - 1016

EP - 1026

JO - Journal of Cachexia, Sarcopenia and Muscle

JF - Journal of Cachexia, Sarcopenia and Muscle

SN - 2190-6009

IS - 5

ER -