Gene therapy for ornithine transcarbamylase deficiency

Ornithine transcarbamylase (OTC) deficiency in humans is the most common and severe inborn error of the urea cycle. Despite therapeutic advances, OTC deficiency remains without adequate treatment, hence mortality rates are high. In the two available strains of OTC-deficient murine models, spf and spf(ask), researchers have tried to make genetic corrections by introducing the OTC gene. Transient but complete recovery of OTC was obtained in adult spf(ask) mice and in OTC-deficient human primary hepatocytes, using a recombinant adenoviral vector. These experiments represent a first step in the development of human gene therapy for OTC deficiency and other hepatic enzyme deficiencies.