{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:23:27Z","timestamp":1777944207416,"version":"3.51.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by SMN gene defects. It leads to motor neuron death and muscle weakness. Without treatment, most affected children don't survive past age two. Recently, new gene therapies help SMA children survive, but treated patients now face ongoing muscle atrophy and functional deficits, creating a novel clinical presentation. Over the last years, treatments of various animal models of neuromuscular disorders have shown the ability of inhibitors of the non-conventional histone deacetylase 6 (HDAC6) to reduce muscle atrophy.<\/jats:p>\n                  <jats:p>This study examines HDAC6 inhibition's impact on muscle cell differentiation and tests in vivo if combining it with new standard SMA treatments improves muscle and overall condition in SMA mice. Here, we report that HDAC6 controls myotube formation and maturation in vitro. In particular, HDAC6 inhibition increases the size of SMA patients-derived muscle primary myotubes. In vivo, when combined with ASOs inducing exon-7 inclusion in SMN2 RNA, HDAC6 systemic inhibition strongly improved muscle strength, mass, function, and longevity of SMA-like mice model.<\/jats:p>\n                  <jats:p>These findings provide evidence that selective inhibition of HDAC6 improves myogenic progression. Hence, HDAC6 inhibitors are good candidates to ameliorate persisting symptoms of SMA patients treated with the new standard of care.<\/jats:p>","DOI":"10.1093\/brain\/awag148","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T12:19:26Z","timestamp":1777637966000},"source":"Crossref","is-referenced-by-count":0,"title":["Combining SMN2 splicing modifiers with HDAC6 inhibition improves spinal muscular atrophy outcomes"],"prefix":"10.1093","author":[{"given":"Alexis","family":"Osseni","sequence":"first","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon1, CNRS UMR 5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) , Lyon ,","place":["France"]},{"name":"Hospices Civils de Lyon, Centre de Biotechnologie Cellulaire , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasha","family":"Slika","sequence":"additional","affiliation":[{"name":"University Paris Cit\u00e9, Inserm UMR_S1124 , 75270, Paris Cedex 06 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Coudert","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon1, CNRS UMR 5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agn\u00e8s","family":"Conjard-Duplany","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon1, CNRS UMR 5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laure","family":"Weill","sequence":"additional","affiliation":[{"name":"University Paris Cit\u00e9, Inserm UMR_S1124 , 75270, Paris Cedex 06 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0496-2309","authenticated-orcid":false,"given":"Edwige","family":"Belotti","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon1, CNRS UMR 5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Siopi","sequence":"additional","affiliation":[{"name":"University Paris Cit\u00e9, Inserm UMR_S1124 , 75270, Paris Cedex 06 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9031-1184","authenticated-orcid":false,"given":"Yann-Ga\u00ebl","family":"Gangloff","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon1, CNRS UMR 5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delphine","family":"Sapaly","sequence":"additional","affiliation":[{"name":"University Paris Cit\u00e9, Inserm UMR_S1124 , 75270, Paris Cedex 06 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Bendris","sequence":"additional","affiliation":[{"name":"University Paris Cit\u00e9, Inserm UMR_S1124 , 75270, Paris Cedex 06 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zo\u00e9","family":"Clerc","sequence":"additional","affiliation":[{"name":"University Paris Cit\u00e9, Inserm UMR_S1124 , 75270, Paris Cedex 06 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ga\u00eblle","family":"Bruneteau","sequence":"additional","affiliation":[{"name":"University Paris Cit\u00e9, Inserm UMR_S1124 , 75270, Paris Cedex 06 ,","place":["France"]},{"name":"Assistance Publique H\u00f4pitaux de Paris, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris ALS expert center, Department of Neurology , Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Vuillerot","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon1, CNRS UMR 5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) , Lyon ,","place":["France"]},{"name":"Centre R\u00e9f\u00e9rent Maladies Rares Neuromusculaires, Service de M\u00e9decine Physique et de R\u00e9adaptation P\u00e9diatrique des Hospices Civils de Lyon - H\u00f4pital Femme M\u00e8re Enfant , Bron ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3214-5880","authenticated-orcid":false,"given":"Pascal","family":"Leblanc","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon1, CNRS UMR 5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Charbonnier","sequence":"additional","affiliation":[{"name":"University Paris Cit\u00e9, Inserm UMR_S1124 , 75270, Paris Cedex 06 ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6600-503X","authenticated-orcid":false,"given":"Laurent","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Claude Bernard Lyon1, CNRS UMR 5261, INSERM U1315, Pathophysiology and Genetics of Neuron and Muscle (INMG-PGNM) , Lyon ,","place":["France"]},{"name":"Hospices Civils de Lyon, Centre de Biotechnologie Cellulaire , Lyon ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,5,2]]},"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag148\/68201904\/awag148.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awag148\/68201904\/awag148.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T07:50:26Z","timestamp":1777708226000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/advance-article\/doi\/10.1093\/brain\/awag148\/8666440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,2]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/brain\/awag148","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,2]]},"article-number":"awag148"}}