Crigler-Najjar Syndrome (CN) is a rare genetic disorder caused by a defect of the UGT1A1 gene, which encodes the protein responsible for metabolizing bilirubin. The resulting toxic accumulation of bilirubin can cause severe neurological impairment and death. Phototherapy can help manage bilirubin levels, but requires 10-12 hour treatments each day and becomes less effective with age, at which point a liver transplant is required. GTP and Audentes are collaborating to advance AAV8-UGT1A1 (AT342) for the treatment of CN. A phase 1/2, multinational, open-label, ascending-dose, delayed-treatment concurrent control clinical study is planned (VALENS; NCT03223194).
Ornithine transcarbamylase (OTC) deficiency is an inherited X-linked genetic disease that causes the ammonia formed when proteins are degraded to accumulate in the blood. A late-onset form of the disease affects both males and females, and can result in altered mental status, headaches, vomiting, and seizures. Treatment includes dietary protein restriction, amino acid supplementation, and nitrogen-scavenging drugs. GTP is supporting Dimension’s development of an AAV8-OTC gene therapy approach (DTX301) for the treatment of this disease, which has advanced to a Phase 1/2 clinical trial (NCT02991144).