Ornithine Transcarbamylase Deficiency Clinical Trial
Ornithine Transcarbamylase Deficiency
A large number of genetic diseases have been described that cause derangements
in metabolic pathways of the liver. A deficiency of the urea cycle enzyme
Ornithine Transcarbamylase (OTC) is a paradigm for such metabolic diseases.
Genes deficient in this enzyme are unable to break down nitrogen, which
leads to an accumulation of such toxic substances as ammonia. Investigators
at the IHGT were recently approved to initiate a Phase I Clinical Trial
to evaluate the utility of gene therapy for treating OTC deficiency.
The general concept involves using a virus as a vehicle to deliver the
normal OTC gene to the liver cells of the patients. A modified version
of the human adenovirus has been created by deleting potential disease-causing
genes and inserting the normal OTC gene. When infused into the blood this
recombinant virus targets the liver cells very specifically and efficiently.
Patients eligible for this clinical trial are adults partially deficient
of OTC. This would include the affected males who live beyond adolescence
and adult carrier females. A total of 18 patients will be enrolled in the
trial. Participating patients are admitted to the Hospital of the University
of Pennsylvania where they undergo a procedure in which a catheter is inserted
into a groin artery and advanced into the vessel that perfuses the liver.
The vector is injected into the catheter thereby targeting the liver. The
patients remain in the hospital for several days can return home after
appropriate follow-up is arranged. This is a dose escalation study in which
the initial patients receive the lowest dose of vector, which is advanced
in subsequent groups pending an evaluation of the safety data.
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