Urea cycle disorders (UCD) are a group of rare genetic disorders afflicting 2,000-6,000 patients in the US. UCDs are caused by a deficiency of one of the six enzymes in the urea cycle, which takes place in the liver. The urea cycle is a series of biochemical steps in which nitrogen, a waste product of protein metabolism, is removed from the blood and converted to a compound called urea. Normally, the urea is transferred into the urine and removed from the body. In people with UCD, the nitrogen accumulates in the form of ammonia, a highly toxic substance, resulting in elevated blood ammonia, or hyperammonemia. If levels of ammonia in the blood become too high, it can reach the brain where it can cause irreversible brain damage, coma and even death. The best available treatment option is a liver transplant.1
In addition to UCD, there are several other disorders that cause hyperammonemia, including other forms of inborn errors of metabolism (~33,000 patients in the US) and hepatic encephalopathy associated with liver damage (~900,000 patients in the US).
SYNB1020 is a synthetic biotic designed to remove excess ammonia from the blood. SYNB1020 operates from the gut microbiome and is engineered to activate a programmed metabolic pathway to remove excess ammonia for the treatment of UCD and other forms of hyperammonemia. By performing these metabolic activities, SYNB1020 reduces abnormal levels of ammonia in the blood, compensating for defects in the intrinsic urea cycle. Our Synthetic BioticTM demonstrates robust reduction in the blood ammonia levels in validated rodent models of hyperammonemia. SYNB1020 has the potential to transform the treatment paradigm for hyperammonemia with a highly differentiated, potentially safe and effective oral once a day medicine. Synlogic is rapidly advancing SYNB1020 toward the clinic with the goal of filing an IND to initiate clinical trials of SYNB1020 in 1H 2017.
1 Content adapted from the National Urea Cycle Disorders Foundation website: http://www.nucdf.org