Enzyme replacement with PEGylated cystathionine beta-synthase ameliorates homocystinuria in murine model

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F16%3A10327105" target="_blank" >RIV/00064165:_____/16:10327105 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/16:10327105

Result on the web

<a href="http://dx.doi.org/10.1172/JCI85396" target="_blank" >http://dx.doi.org/10.1172/JCI85396</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1172/JCI85396" target="_blank" >10.1172/JCI85396</a>

Result language

angličtina

Original language name

Enzyme replacement with PEGylated cystathionine beta-synthase ameliorates homocystinuria in murine model

Original language description

Homocystinuria, which typically results from cystathionine beta-synthase (CBS) deficiency, is the most common defect of sulfur amino acid metabolism. CBS condenses homocysteine and serine to cystathionine that is then converted to cysteine. Individuals with homocystinuria have markedly elevated plasma levels of homocysteine and methionine and reduced concentrations of cystathionine and cysteine. Clinical disease manifestations include thromboembolism and neuropsychiatric, ocular, and skeletal complications. Here, we have shown that administration of PEGylated CBS into the circulation of homocystinuria model mice alters the extra-and intracellular equilibrium of sulfur amino acids, resulting in a decrease of approximately 75% in plasma total homocysteine (tHcy) and normalization of cysteine concentrations. Moreover, the decrease in homocysteine and the normalization of cysteine in PEGylated CBS-treated model mice were accompanied by improvement of histopathological liver symptoms and increased survival. Together, these data suggest that CBS enzyme replacement therapy (ERT) is a promising approach for the treatment of homocystinuria and that ERT for metabolic diseases may not necessitate introduction of the deficient enzyme into its natural intracellular compartment.

Czech name

—

Czech description

—

Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

—

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Clinical Investigation

ISSN

0021-9738

e-ISSN

—

Volume of the periodical

126

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

2372-2384

UT code for WoS article

000377027500032

EID of the result in the Scopus database

2-s2.0-84974574111