Enzyme Replacement Therapy Ameliorates Multiple Symptoms of Murine Homocystinuria
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10376633" target="_blank" >RIV/00216208:11110/18:10376633 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/18:10376633
Result on the web
<a href="https://doi.org/10.1016/j.ymthe.2017.12.014" target="_blank" >https://doi.org/10.1016/j.ymthe.2017.12.014</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ymthe.2017.12.014" target="_blank" >10.1016/j.ymthe.2017.12.014</a>
Alternative languages
Result language
angličtina
Original language name
Enzyme Replacement Therapy Ameliorates Multiple Symptoms of Murine Homocystinuria
Original language description
Classical homocystinuria (HCU) is the most common inherited disorder of sulfur amino acid metabolism caused by deficiency in cystathionine beta-synthase (CBS) activity and characterized by severe elevation of homocysteine in blood and tissues. Treatment with dietary methionine restriction is not optimal, and poor compliance leads to serious complications. We developed an enzyme replacement therapy (ERT) and studied its efficacy in a severe form of HCU in mouse (the I278T model). Treatment was initiated before or after the onset of clinical symptoms in an effort to prevent or reverse the phenotype. ERT substantially reduced and sustained plasma homocysteine concentration at around 100 mu M and normalized plasma cysteine for up to 9 months of treatment. Biochemical balance was also restored in the liver, kidney, and brain. Furthermore, ERT corrected liver glucose and lipid metabolism. The treatment prevented or reversed facial alopecia, fragile and lean phenotype, and low bone mass. In addition, structurally defective ciliary zonules in the eyes of I278T mice contained low density and/or broken fibers, while administration of ERT from birth partially rescued the ocular phenotype. In conclusion, ERT maintained an improved metabolic pattern and ameliorated many of the clinical complications in the I278T 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
30202 - Endocrinology and metabolism (including diabetes, hormones)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Therapy
ISSN
1525-0016
e-ISSN
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Volume of the periodical
26
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
834-844
UT code for WoS article
000427911800020
EID of the result in the Scopus database
2-s2.0-85041575546