Recombinant adenovirus gene transfer in adults with partial ornithine transcarbamylase deficiency (OTCD)

Ornithine transcarbamylase (OTC), a mitochondrial matrix enzyme, is the second enzyme in the urea cycle. Deficient liver OTC activity results in accumulation of ammonia in blood and brain with resultant encephalopathy. Other biochemical abnormalities include accumulations of glutamine in blood and of orotic acid in urine behind the enzyme block. Glutamine and orotic acid prove to be useful indicators of OTC deficiency (OTCD) and will be used as a measure of efficacy of gene therapy. Stable isotope studies have also proven helpful in assessing residual urea synthetic capacity. The rate of flux through the urea cycle is measured by administering orally super(15)NH sub(4)Cl and measuring appearance of super(15)N urea in blood and urine. We have performed these stable isotope studies in 20 controls and OTCD patients and found it to be a sensitive in vivo indicator of residual OTC activity. OTCD is ideally suited for treatment using in vivo gene therapy to restore partial OTC activity to the patient.