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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
ID Deutsch, Leon (Avtor), ID Osredkar, Damjan (Avtor), ID Plavec, Janez (Avtor), ID Stres, Blaž (Avtor)

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Izvleček
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.

Jezik:Angleški jezik
Ključne besede:spinal muscular atrophy, nusinersen, therapy, healthy control cohort, 1H-NMR metabolomics, males, females, serum, liquor, urine
Vrsta gradiva:Članek v reviji (dk_c)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:BF - Biotehniška fakulteta
MF - Medicinska fakulteta
FGG - Fakulteta za gradbeništvo in geodezijo
Leto izida:2021
Status objave pri reviji:Objavljeno
Verzija članka:Založnikova različica članka
Št. strani:15 str.
Številčenje:Vol. 11, iss. 4, art. 206
UDK:616.8
ISSN pri članku:2218-1989
DOI:10.3390/metabo11040206 Povezava se odpre v novem oknu
COBISS.SI-ID:57724931 Povezava se odpre v novem oknu
Datum objave v RUL:16.02.2022
Število ogledov:142
Število prenosov:56
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Gradivo je del revije

Naslov:Metabolites
Skrajšan naslov:Metabolites
Založnik:MDPI
ISSN:2218-1989
COBISS.SI-ID:523274009 Povezava se odpre v novem oknu

Licence

Licenca:CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:01.04.2021

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:mišična atrofija hrbtenice, nusinersen, terapija, zdrava nadzorna kohorta

Gradivo je financirano iz projekta

Financer:Drugi - Drug financer ali več financerjev
Program financ.:University Medical Centre Ljubljana
Številka projekta:20200010

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Številka projekta:P3-0343
Naslov:Etiologija, zgodnje odkrivanje in zdravljenje bolezni pri otrocih in mladostnikih

Financer:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Program financ.:Young Researcher

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