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

Pradeep Harish, Alberto Malerba, Ngoc Lu-Nguyen, Leysa Forrest, Ornella Cappellari, Fanny Roth, Capucine Trollet, Linda Popplewell, George Dickson

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)1016-1026
Number of pages11
JournalJournal of Cachexia, Sarcopenia and Muscle
Issue number5
Early online date7 May 2019
Publication statusPublished - Oct 2019

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