Phenylketonuria (PKU) is a rare genetic disorder afflicting approximately 13,000 people in the US and is caused by mutations in the gene encoding the enzyme phenylalanine hydroxylase (PAH). This enzyme resides in the liver and is necessary to convert phenylalanine, an amino acid, into another amino acid called tyrosine after protein is eaten. Due to the PAH enzyme deficiency, PKU patients cannot breakdown phenylalanine resulting in accumulation that can cause severe mental retardation and other central nervous system disorders. There remains significant unmet need for people with PKU who must adhere to a lifelong, extremely low-protein diet that can result in serious developmental disorders.1 Our Lead PKU program is a Synthetic BioticTM designed to remove excess phenylalanine from the blood. It is engineered to activate a programmed metabolic pathway to degrade phenylalanine and compensate for the missing phenylalanine hydroxylase activity in the liver. Our Synthetic BioticTM has demonstrated robust activity in validated rodent models of PKU. It has the potential to transform the treatment paradigm for PKU as a highly differentiated, potentially safe and effective oral therapy.Synlogic is rapidly advancing our Lead PKU program into development with the goal of filing an IND to initiate clinical trials in the next 12 months.
1 Content adapted from the PKU Foundation website: https://www.pkufoundation.com