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Nusinersen has improved ventilator\u2010free survival and motor function outcomes in infantile onset forms of spinal muscular atrophy (SMA), treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation. Therefore, we aimed to identify novel noninvasive biomarkers that could predict the response to nusinersen in type II and III SMA patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty\u2010four SMA patients were included. We applied next generation sequencing to identify microRNAs in the cerebrospinal fluid (CSF) as candidate biomarkers predicting response to nusinersen. Hammersmith Functional Motor Scale Expanded (HFMSE) was conducted at baseline and 6\u00a0months after initiation of nusinersen therapy to assess motor function. Patients changing by \u22653 or \u22640 points in the HFMSE total score were considered to be responders or nonresponders, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Lower baseline levels of two muscle microRNAs (miR\u2010206 and miR\u2010133a\u20103p), alone or in combination, predicted the clinical response to nusinersen after 6\u00a0months of therapy. Moreover, miR\u2010206 levels were inversely correlated with the HFMSE score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lower miR\u2010206 and miR\u2010133a\u20103p in the CSF predict more robust clinical response to nusinersen treatment in later onset SMA patients. These novel findings have high clinical relevance for identifying early treatment response to nusinersen in later onset SMA patients and call for testing the ability of miRNAs to predict more sustained long\u2010term benefit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.15382","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T07:25:59Z","timestamp":1651735559000},"page":"2420-2430","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-3175","authenticated-orcid":false,"given":"Iddo","family":"Magen","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics Weizmann Institute of Science Rehovot Israel"},{"name":"Department of Molecular Neuroscience Weizmann Institute of Science Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7255-6276","authenticated-orcid":false,"given":"Sharon","family":"Aharoni","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Neurology Schneider Children's Medical Center of Israel Petach Tikva Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy Sarah","family":"Yacovzada","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics Weizmann Institute of Science Rehovot Israel"},{"name":"Department of Molecular Neuroscience Weizmann Institute of Science Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itay","family":"Tokatly Latzer","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel"},{"name":"Pediatric Neurology Institute Dana\u2010Dwek Children's Hospital Tel Aviv Medical Center Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiano R. 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