20.500.12556/RUL-134992 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 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. spinal muscular atrophy nusinersen therapy healthy control cohort 1H-NMR metabolomics males females serum liquor urine mišična atrofija hrbtenice nusinersen terapija zdrava nadzorna kohorta true false true Angleški jezik Slovenski jezik Članek v reviji 2022-02-16 13:41:47 2022-02-16 13:41:55 2022-09-14 04:11:04 0000-00-00 00:00:00 2021 0 0 15 str. iss. 4, art. 206 Vol. 11 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.8 2218-1989 10.3390/metabo11040206 57724931 RAZ_Deutsch_Leon_2021.pdf RAZ_Deutsch_Leon_2021.pdf 1 53E33696D798EBE1D438DD504AE5C930 e376e388320f5818bdafd20737efd8b6da5ce85442d8b5cc2fd9d315d95d5ce5 d2952910-8f25-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153794 https://www.mdpi.com/2218-1989/11/4/206 1 94be682f-8f25-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=153793 Biotehniška fakulteta Medicinska fakulteta Fakulteta za gradbeništvo in geodezijo 0 0 0