{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:53:31Z","timestamp":1790780011832,"version":"4.1.0"},"reference-count":44,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["SNF 310030_184765"],"award-info":[{"award-number":["SNF 310030_184765"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss Muscle Foundation","award":["FRSMM"],"award-info":[{"award-number":["FRSMM"]}]},{"DOI":"10.13039\/501100008038","name":"NeRAB","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008038","id-type":"DOI","asserted-by":"crossref"}]},{"name":"RYR1 Foundation"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,2,18]]},"abstract":"<jats:p>\n                    To date there are no therapies for patients with congenital myopathies, muscle disorders causing poor quality of life of affected individuals. In approximately 30% of the cases, patients with congenital myopathies carry either dominant or recessive mutations in the ryanodine receptor 1 (\n                    <jats:italic>RYR1<\/jats:italic>\n                    ) gene; recessive\n                    <jats:italic>RYR1<\/jats:italic>\n                    mutations are accompanied by reduction of RyR1 expression and content in skeletal muscles and are associated with fiber hypotrophy and muscle weakness. Importantly, muscles of patients with recessive\n                    <jats:italic>RYR1<\/jats:italic>\n                    mutations exhibit increased content of class II histone deacetylases and of DNA genomic methylation. We recently created a mouse model knocked-in for the p.Q1970fsX16+ p.A4329D RyR1 mutations, which are isogenic to those carried by a severely affected child suffering from a recessive form of RyR1-related multi-mini core disease. The phenotype of the RyR1 mutant mice recapitulates many aspects of the clinical picture of patients carrying recessive\n                    <jats:italic>RYR1<\/jats:italic>\n                    mutations. We treated the compound heterozygous mice with a combination of two drugs targeting DNA methylases and class II histone deacetylases. Here, we show that treatment of the mutant mice with drugs targeting epigenetic enzymes improves muscle strength, RyR1 protein content, and muscle ultrastructure. This study provides proof of concept for the pharmacological treatment of patients with congenital myopathies linked to recessive\n                    <jats:italic>RYR1<\/jats:italic>\n                    mutations.\n                  <\/jats:p>","DOI":"10.7554\/elife.73718","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T08:00:40Z","timestamp":1646294440000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.73718","source":"Crossref","is-referenced-by-count":16,"title":["Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors"],"prefix":"10.7554","volume":"11","author":[{"given":"Alexis","family":"Ruiz","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04k51q396","id-type":"ROR","asserted-by":"publisher"}],"name":"Neuromuscular Research Group, Departments of Neurology and Biomedicine, Basel University Hospital","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Benucci","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04k51q396","id-type":"ROR","asserted-by":"publisher"}],"name":"Neuromuscular Research Group, Departments of Neurology and Biomedicine, Basel University Hospital","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7811-3932","authenticated-orcid":true,"given":"Urs","family":"Duthaler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04k51q396","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Clinical Pharmacology & Toxicology, Department of Biomedicine, University and University Hospital Basel","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Bachmann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04k51q396","id-type":"ROR","asserted-by":"publisher"}],"name":"Neuromuscular Research Group, Departments of Neurology and Biomedicine, Basel University Hospital","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Franchini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04k51q396","id-type":"ROR","asserted-by":"publisher"}],"name":"Neuromuscular Research Group, Departments of Neurology and Biomedicine, Basel University Hospital","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiza","family":"Noreen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Genome plasticity group, Department of Biomedicine, University of Basel","place":["Basel, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pietrangelo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qjgza05","id-type":"ROR","asserted-by":"publisher"}],"name":"CAST, Center for Advanced Studies and Technology & DMSI, Dept. of Neuroscience, Imaging and Clinical Sciences, Univ. 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