CONTACT:
Jennifer Hastings, (215) 895-3681;
or Jennifer Donovan, (504) 670-8503
GENE THERAPY SUCCESSFULLY ADMINISTERED THROUGH BLOOD STREAM
Philadelphia, Pa. -- A breakthrough study on in vivo gene therapy may someday provide the medical know-how to eliminate inherited metabolic disorders.
The study was developed through a joint effort between the child development and rehabilitation hospital Children's Seashore House and the University of Pennsylvania School of Medicine. The research team is comprised of Mark Batshaw, M.D.; Marc Yudkoff, M.D.; and Michael Robinson, Ph.D., all of Children's Seashore House; along with James Wilson, M.D., Ph.D., director of the Institute for Human Gene Therapy at the University of Pennsylvania.
Dr. Batshaw, physician-in-chief at Children's Seashore House, will present his abstract on the study, "Measuring Ureagenesis In Vivo with Stable Isotopes Provides a Tool to Assess Efficacy of Gene Therapy," at the Pediatric Academic Societies' Annual Meeting on May 4, in New Orleans, La.
Funded by a five-year, $4 million grant from the National Institutes of Health (NIH), the therapy seeks to ultimately cure Ornithine Transcarbamylase Deficiency (OTCD), a rare inborn error in metabolism. Those with OTCD are born with deficient OTC enzyme activity. OTC is one of the five enzymes in the liver needed for the body to convert ammonia, a breakdown of the protein we eat, to urea. Without the OTC enzyme, dangerous levels of ammonia build up, leading to a coma, severe brain damage, or death.
"OTCD is an excellent model to study gene therapy," says Dr. Batshaw. "The disorder is relatively frequent -- about 100 children are born with OTCD each year; the gene has been cloned; and the OTC enzyme is located in the liver, making it readily accessible to gene transfer. There is also an animal model to test -- the sparse fur mouse."
In gene therapy, normal copies of the OTC gene are injected into the blood stream so the new gene will serve as a blueprint to produce normal levels of OTC and correct the enzyme deficiency. The advantage of in vivo gene therapy is that no surgical procedure is needed to inject the engineered gene, and virtually 100 percent of the liver cells can be affected by the treatment.
OTC deficient sparse fur mice were used to test gene therapy before clinical trials on humans were initiated. The therapy increased ammonia incorporation into urea by 22 percent seven days after treatment. Fourteen days after gene transfer, it was increased by 52 percent.
In 1997, permission was granted by the Food and Drug Administration for the first phase of human trials in gene therapy. In a groundbreaking move, the research team is currently administering gene therapy to adults with partial OTC deficiency to test its safety before trying it on severely affected children.
Dr. Batshaw reports, "Early results are promising; we are hopeful of moving on to gene therapy for children with severe OTCD."
Founded in 1872, Children's Seashore House is a 77-bed regional teaching hospital providing specialized care and rehabilitation for children with developmental disabilities and chronic illnesses.
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