Phase I Study of Adenoviral Vector Mediated Gene Transfer for Ornithine Transcarbamylase in Adults With Partial Ornithine Transcarbamylase Deficiency

OBJECTIVES:

I. Determine the safety, feasibility, and potential efficacy of intravascular adenoviral vector mediated gene transfer in the liver in adults with partial ornithine transcarbamylase deficiency.

PROTOCOL OUTLINE: This is a dose escalation study. Patients undergo a femoral arterial placement of a hepatic intraarterial catheter. Patients then receive adenoviral vector mediated gene transfer intravascularly over 30 minutes.

Cohorts of 3 patients each receive escalating doses of adenoviral vector until the maximum tolerated dose is determined.

Patients are followed at 3, 5, 7, 8, 15, and 29 days, at 2 months, and then every 3 months thereafter.

Completion date provided represents the completion date of the grant per OOPD records

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of partial ornithine transcarbamylase deficiency Female heterozygote with abnormal allopurinol challenge or underlying defect in either N15 urea or N15 glutamine OR Male with childhood/adulthood onset OR Family history of 2 affected children
• Stable for at least 1 month prior to study
• Plasma ammonium levels less than 50 micromoles

--Prior/Concurrent Therapy--

• Concurrent alternate pathway therapy to control hyperammonemia allowed

--Patient Characteristics--

• Hepatic: No history of liver disease
• Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No high level of neutralizing antibodies to the adenovirus