{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:13:47Z","timestamp":1777029227250,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["P3-0343"],"award-info":[{"award-number":["P3-0343"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["R#51867"],"award-info":[{"award-number":["R#51867"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Medical Centre Ljubljana","award":["20200010"],"award-info":[{"award-number":["20200010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a genetically heterogeneous group of rare neuromuscular diseases and was until recently the most common genetic cause of death in children. The effects of 2-month nusinersen therapy on urine, serum, and liquor 1H-NMR metabolomes in SMA males and females were not explored yet, especially not in comparison to the urine 1H-NMR metabolomes of matching male and female cohorts. In this prospective, single-centered study, urine, serum, and liquor samples were collected from 25 male and female pediatric patients with SMA before and after 2 months of nusinersen therapy and urine samples from a matching healthy cohort (n = 125). Nusinersen intrathecal application was the first therapy for the treatment of SMA by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Metabolomes were analyzed using targeted metabolomics utilizing 600 MHz 1H-NMR, parametric and nonparametric multivariate statistical analyses, machine learning, and modeling. Medical assessment before and after nusinersen therapy showed significant improvements of movement, posture, and strength according to various medical tests. No significant differences were found in metabolomes before and after nusinersen therapy in urine, serum, and liquor samples using an ensemble of statistical and machine learning approaches. In comparison to a healthy cohort, 1H-NMR metabolomes of SMA patients contained a reduced number and concentration of urine metabolites and differed significantly between males and females as well. Significantly larger data scatter was observed for SMA patients in comparison to matched healthy controls. Machine learning confirmed urinary creatinine as the most significant, distinguishing SMA patients from the healthy cohort. The positive effects of nusinersen therapy clearly preceded or took place devoid of significant rearrangements in the 1H-NMR metabolomic makeup of serum, urine, and liquor. Urine creatinine was successful at distinguishing SMA patients from the matched healthy cohort, which is a simple systemic novelty linking creatinine and SMA to the physiology of inactivity and diabetes, and it facilitates the monitoring of SMA disease in pediatric patients through non-invasive urine collection.<\/jats:p>","DOI":"10.3390\/metabo11040206","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T09:57:04Z","timestamp":1617098224000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Spinal Muscular Atrophy after Nusinersen Therapy: Improved Physiology in Pediatric Patients with No Significant Change in Urine, Serum, and Liquor 1H-NMR Metabolomes in Comparison to an Age-Matched, Healthy Cohort"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3739-8142","authenticated-orcid":false,"given":"Leon","family":"Deutsch","sequence":"first","affiliation":[{"name":"Department of Animal Science, Biotechnical Faculty, University of Ljubljana, SI-1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-420X","authenticated-orcid":false,"given":"Damjan","family":"Osredkar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, University Children\u2019s Hospital, University Medical Centre Ljubljana, SI-1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1570-8602","authenticated-orcid":false,"given":"Janez","family":"Plavec","sequence":"additional","affiliation":[{"name":"National Institute of Chemistry, NMR Center, SI-1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2972-2907","authenticated-orcid":false,"given":"Bla\u017e","family":"Stres","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Biotechnical Faculty, University of Ljubljana, SI-1000 Ljubljana, Slovenia"},{"name":"Department of Automation, Biocybernetics and Robotics, Jo\u017eef Stefan Institute, SI-1000 Ljubljana, Slovenia"},{"name":"Faculty of Civil and Geodetic Engineering, Institute of Sanitary Engineering, University of Ljubljana, SI-1000 Ljubljana, Slovenia"},{"name":"Department of Microbiology, University of Innsbruck, A-6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"ref_1","unstructured":"Sumner, C.J., Paushkin, S., and Ko, C. 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