An engineered E. coli Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans

作者：Caroline Kurtz, Yves Millet, Marja Puurunen, Mylène Perreault, Mark R. Charbonneau, Vincent M. Isabella, Jonathan W. Kotula, Eugene Antipov, Yossi Dagon, William S. Denney, David A. Wagner, Kip A. West, Andrew J. Degar, Aoife M. Brennan, Paul Miller · 发表于：Science Translational Medicine · 年份：2019 · DOI：10.1126/scitranslmed.aau7975 · 被引用次数：403 · 研究领域：Metabolism and Genetic Disorders、Diet and metabolism studies、Clinical Nutrition and Gastroenterology

N-nitrate was demonstrated, indicating in vivo SYNB1020 activity. SYNB1020 concentrations reached steady state by the second day of dosing, and excreted cells were alive and metabolically active as evidenced by fecal arginine production in response to added ammonium chloride. SYNB1020 was no longer detectable in feces 2 weeks after the last dose. These results support further clinical development of SYNB1020 for hyperammonemia disorders including urea cycle disorders and hepatic encephalopathy.