Enzyme replacement prevents neonatal death, liver damage, and osteoporosis in murine homocystinuria

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10366201" target="_blank" >RIV/00216208:11110/17:10366201 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/17:10366201

Výsledek na webu

<a href="http://dx.doi.org/10.1096/fj.201700565R" target="_blank" >http://dx.doi.org/10.1096/fj.201700565R</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1096/fj.201700565R" target="_blank" >10.1096/fj.201700565R</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Enzyme replacement prevents neonatal death, liver damage, and osteoporosis in murine homocystinuria

Popis výsledku v původním jazyce

Classical homocystinuria (HCU) is an inborn error of sulfur amino acidmetabolism caused by deficient activity of cystathionine beta-synthase (CBS), resulting in an accumulation of homocysteine and a concomitant decrease of cystathionine and cysteine in blood and tissues. In mice, the complete lack of CBS is neonatally lethal. In this study, newborn CBS-knockout (KO) mice were treated with recombinant polyethyleneglycolylated human truncatedCBS (PEG-CBS). Full survival of the treatedKOmice, along with a positive impact on metabolite levels in plasma, liver, brain, and kidneys, was observed. The PEG-CBS treatment prevented an otherwise fatal liver disease characterized by steatosis, death of hepatocytes, and ultrastructural abnormalities of endoplasmic reticulum andmitochondria. Furthermore, treatment of the KO mice for 5mo maintained the plasma metabolite balance and completely prevented osteoporosis and changes in body composition that characterize both the KO model and human patients. These findings argue that early treatment of patients with HCU with PEG-CBSmay prevent clinical symptoms of the disease possibly without the need of dietary protein restriction.

Název v anglickém jazyce

Enzyme replacement prevents neonatal death, liver damage, and osteoporosis in murine homocystinuria

Popis výsledku anglicky

Classical homocystinuria (HCU) is an inborn error of sulfur amino acidmetabolism caused by deficient activity of cystathionine beta-synthase (CBS), resulting in an accumulation of homocysteine and a concomitant decrease of cystathionine and cysteine in blood and tissues. In mice, the complete lack of CBS is neonatally lethal. In this study, newborn CBS-knockout (KO) mice were treated with recombinant polyethyleneglycolylated human truncatedCBS (PEG-CBS). Full survival of the treatedKOmice, along with a positive impact on metabolite levels in plasma, liver, brain, and kidneys, was observed. The PEG-CBS treatment prevented an otherwise fatal liver disease characterized by steatosis, death of hepatocytes, and ultrastructural abnormalities of endoplasmic reticulum andmitochondria. Furthermore, treatment of the KO mice for 5mo maintained the plasma metabolite balance and completely prevented osteoporosis and changes in body composition that characterize both the KO model and human patients. These findings argue that early treatment of patients with HCU with PEG-CBSmay prevent clinical symptoms of the disease possibly without the need of dietary protein restriction.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

The FASEB Journal

ISSN

0892-6638

e-ISSN

—

Svazek periodika

31

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

5495-5506

Kód UT WoS článku

000416588300031

EID výsledku v databázi Scopus

2-s2.0-85036568932