An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria. Issue 3 (7th March 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Molecular systems biology. Volume 18:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-07
• Subjects: engineered bacteria -- enteric hyperoxaluria -- in silico modeling -- oxalate -- synthetic biology; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.202110539
• Languages: English
• ISSNs: 1744-4292

Abstract

Abstract: 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. SYNOPSIS: SYNB8802 is an engineered probiotic designed to metabolize oxalate in patients with enteric hyperoxaluria. The strain shows significant oxalate degradation in vitro and in vivo, and in silico modeling predicts that it can lower urinary oxalate in patients. Enteric hyperoxaluria is a metabolic disorder where oxalate overabsorption can lead to chronic kidney stones and ultimately kidney failure. SYNB8802 is an engineered probiotic, derived from Escherichia coli Nissle capable of degrading oxalate. SYNB8802 lowers urinary oxalate, a disease biomarker, as shown in preclinical data from mice and non‐human primates. In silico modeling predicts that SYNB8802 lowers urinary oxalate up to 71% in patients. Abstract : SYNB8802 is an engineered probiotic designed to metabolize oxalate in patients with enteric hyperoxaluria. The strain shows significant oxalate degradation in vitro and in vivo, and in silico modeling predicts that it can lower urinary oxalate in patients.