Gene therapy cures inherited liver disease in rats

A single dose of gene-virus combination cured rats of a inherited liver disease in which lack of a gene causes the accumulation of bilirubin –which, untreated, results in jaundice and brain damage, said researchers at Baylor College of Medicine in a report in the Proceedings of the Natural Academy of Sciences.

“This is the first time this disease (Crigler-Najjar syndrome) has been completely cured long term with a single injection in an adult animal,” said Dr. Brendan Lee, associate professor of molecular and human genetics and a Howard Hughes Medical Investigator at Baylor College of Medicine. Crigler-Najjar syndrome is currently treated by placing the person under special UV lights. It is an unwieldy and time-consuming treatment.

While Lee does not think that cure would be possible in all adults with this technique, he does think it poses a real promise for long-term alleviations of the toxic symptoms of these kinds of diseases. The treatment could be repeated when needed.

The treatment used a specially developed adenovirus to carry the gene into the animal’s cells. This viral vector, as it is called, was manipulated so that it minimized toxic side effects. This disease involved a lack of a gene that is found in the part of the cell where detoxification occurs. It points the way to using gene therapy to cure and/or treat a host of other disease that occur because of the lack of genes in this area of the cell.

The viral vector itself is important because it has no long term effect. It does not become part of the genetic machinery of the cell and poses no risk of causing cancer, said Lee. “This approach would be applicable to many diseases where you are trying to put something back, targeting the liver,” he said.

He is hesitant to predict when the treatment can be tried in humans. While the viral vector is fairly benign long term, he would like to see one developed that minimizes the body’s immune response to it immediately right after it is injected into the body.

“Fifteen years ago, the goal was to get some correction of the problem,” he said. “Most effects were transient. Now with these vectors, long-term correction with no long-term toxicity is possible. We need to find a way to avoid short term toxicity.”