Long-term uninterrupted enzyme replacement therapy prevents liver disease in murine model of severe homocystinuria
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10414357" target="_blank" >RIV/00216208:11110/20:10414357 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/20:10414357
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Htd6xJgsTd" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Htd6xJgsTd</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/humu.24072" target="_blank" >10.1002/humu.24072</a>
Alternative languages
Result language
angličtina
Original language name
Long-term uninterrupted enzyme replacement therapy prevents liver disease in murine model of severe homocystinuria
Original language description
Classical homocystinuria (HCU) is an inborn error of metabolism caused by loss of cystathionine beta-synthase (CBS) activity with the concomitant buildup of homocysteine. In knockout (KO) mice, a mouse model of HCU, complete lack of CBS is neonatally lethal. Administration of OT-58, an enzyme therapy for HCU, during the first 5 weeks of life rescued KO mice survival by preventing liver disease. Here, we studied the impact of a long-term uninterrupted OT-58 treatment or its absence beyond the neonatal period on liver pathology and metabolism. Plasma and liver metabolites of KO mice on OT-58 treatment were substantially improved or normalized compared with those receiving vehicle. Increased plasma activities of alanine aminotransferase and aspartate aminotransferase of vehicle-injected KO mice suggested the progression of liver damage with age and lack of treatment. At 3 months of age, liver histology showed no signs of hepatopathy in both vehicle- and OT-58-treated KO mice. However, moderate to severe liver disease, characterized by steatosis, hepatocellular necroses, disorganized endoplasmic reticulum, and swollen mitochondria, developed in 6-month-old vehicle-injected KO mice. KO mice on OT-58 treatment remained asymptomatic and were indistinguishable from age-matched healthy controls. Long-term uninterrupted OT-58 treatment was essential to prevent severe liver disease in the KO mouse model of HCU.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA19-08786S" target="_blank" >GA19-08786S: Interactions between sulfur metabolism and mitochondrial bioenergetics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Human Mutation
ISSN
1059-7794
e-ISSN
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Volume of the periodical
41
Issue of the periodical within the volume
9
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
1662-1670
UT code for WoS article
000548327500001
EID of the result in the Scopus database
2-s2.0-85087894957