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An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria

Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalat...

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Autores principales: Lubkowicz, David, Horvath, Nicholas G, James, Michael J, Cantarella, Pasquale, Renaud, Lauren, Bergeron, Christopher G, Shmueli, Ron B, Anderson, Cami, Gao, Jian‐Rong, Kurtz, Caroline B, Perreault, Mylene, Charbonneau, Mark R, Isabella, Vincent M, Hava, David L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899768/
https://www.ncbi.nlm.nih.gov/pubmed/35253995
http://dx.doi.org/10.15252/msb.202110539
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author Lubkowicz, David
Horvath, Nicholas G
James, Michael J
Cantarella, Pasquale
Renaud, Lauren
Bergeron, Christopher G
Shmueli, Ron B
Anderson, Cami
Gao, Jian‐Rong
Kurtz, Caroline B
Perreault, Mylene
Charbonneau, Mark R
Isabella, Vincent M
Hava, David L
author_facet Lubkowicz, David
Horvath, Nicholas G
James, Michael J
Cantarella, Pasquale
Renaud, Lauren
Bergeron, Christopher G
Shmueli, Ron B
Anderson, Cami
Gao, Jian‐Rong
Kurtz, Caroline B
Perreault, Mylene
Charbonneau, Mark R
Isabella, Vincent M
Hava, David L
author_sort Lubkowicz, David
collection PubMed
description Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalate in the gut and lower urinary oxalate as a potential treatment for EH. Oral administration of SYNB8802 leads to significantly decreased urinary oxalate excretion in healthy mice and non‐human primates, demonstrating the strain's ability to consume oxalate in vivo. A mathematical modeling framework was constructed that combines in vitro and in vivo preclinical data to predict the effects of SYNB8802 administration on urinary oxalate excretion in humans. Simulations of SYNB8802 administration predict a clinically meaningful lowering of urinary oxalate excretion in healthy volunteers and EH patients. Together, these findings suggest that SYNB8802 is a promising treatment for EH.
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spelling pubmed-88997682022-03-15 An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria Lubkowicz, David Horvath, Nicholas G James, Michael J Cantarella, Pasquale Renaud, Lauren Bergeron, Christopher G Shmueli, Ron B Anderson, Cami Gao, Jian‐Rong Kurtz, Caroline B Perreault, Mylene Charbonneau, Mark R Isabella, Vincent M Hava, David L Mol Syst Biol Articles Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalate in the gut and lower urinary oxalate as a potential treatment for EH. Oral administration of SYNB8802 leads to significantly decreased urinary oxalate excretion in healthy mice and non‐human primates, demonstrating the strain's ability to consume oxalate in vivo. A mathematical modeling framework was constructed that combines in vitro and in vivo preclinical data to predict the effects of SYNB8802 administration on urinary oxalate excretion in humans. Simulations of SYNB8802 administration predict a clinically meaningful lowering of urinary oxalate excretion in healthy volunteers and EH patients. Together, these findings suggest that SYNB8802 is a promising treatment for EH. John Wiley and Sons Inc. 2022-03-07 /pmc/articles/PMC8899768/ /pubmed/35253995 http://dx.doi.org/10.15252/msb.202110539 Text en © 2022 Synlogic. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Lubkowicz, David
Horvath, Nicholas G
James, Michael J
Cantarella, Pasquale
Renaud, Lauren
Bergeron, Christopher G
Shmueli, Ron B
Anderson, Cami
Gao, Jian‐Rong
Kurtz, Caroline B
Perreault, Mylene
Charbonneau, Mark R
Isabella, Vincent M
Hava, David L
An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria
title An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria
title_full An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria
title_fullStr An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria
title_full_unstemmed An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria
title_short An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria
title_sort engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899768/
https://www.ncbi.nlm.nih.gov/pubmed/35253995
http://dx.doi.org/10.15252/msb.202110539
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