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dc.contributor.authorLong, Kimberly K.
dc.contributor.authorO'Shea, Karen M.
dc.contributor.authorStains, Joseph P.
dc.creatorLong, K.
dc.date.accessioned2019-04-02T14:58:55Z
dc.date.available2019-04-02T14:58:55Z
dc.date.issued2019-04-01
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063258810&origin=inward
dc.identifier.urihttp://hdl.handle.net/10713/8739
dc.description.abstractSpinal muscular atrophy (SMA) is a neuromuscular disease characterized by loss of α-motor neurons, leading to profound skeletal muscle atrophy. Patients also suffer from decreased bone mineral density and increased fracture risk. The majority of treatments for SMA, approved or in clinic trials, focus on addressing the underlying cause of disease, insufficient production of full-length SMN protein. While restoration of SMN has resulted in improvements in functional measures, significant deficits remain in both mice and SMA patients following treatment. Motor function in SMA patients may be additionally improved by targeting skeletal muscle to reduce atrophy and improve muscle strength. Inhibition of myostatin, a negative regulator of muscle mass, offers a promising approach to increase muscle function in SMA patients. Here we demonstrate that muSRK-015P, a monoclonal antibody which specifically inhibits myostatin activation, effectively increases muscle mass and function in two variants of the pharmacological mouse model of SMA in which pharmacologic restoration of SMN has taken place either 1 or 24 days after birth to reflect early or later therapeutic intervention. Additionally, muSRK-015P treatment improves the cortical and trabecular bone phenotypes in these mice. These data indicate that preventing myostatin activation has therapeutic potential in addressing muscle and bone deficiencies in SMA patients. An optimized variant of SRK-015P, SRK-015, is currently in clinical development for treatment of SMA. © The Author(s) 2018.en_US
dc.description.sponsorshipFunding: SMA Foundation and Scholar Rock to Myologica LLC (to K.O. and R.K.).en_US
dc.description.urihttps://dx.doi.org/10.1093/hmg/ddy382en_US
dc.language.isoen_USen_US
dc.publisherOxford University Press.en_US
dc.relation.ispartofHuman molecular genetics
dc.subject.meshMuscle, Skeletalen_US
dc.subject.meshMuscular Atrophy, Spinal--drug therapyen-US
dc.subject.meshMyostatinen_US
dc.subject.meshMiceen_US
dc.titleSpecific inhibition of myostatin activation is beneficial in mouse models of SMA therapyen_US
dc.typeArticleen_US
dc.identifier.doi10.1093/hmg/ddy382
dc.identifier.pmid30481286
dc.relation.volume28


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