Gene Therapy Cures Inherited Liver Disease in Animals
Single injection completely reverses syndrome currently treated with special lights
3/8/2005 2:25 PM A single injection has completely cured rats of an inherited liver disease that can lead to jaundice and brain damage. The disease, Crigler-Najjar Syndrome, is an inherited metabolic disorder caused by a liver enzyme deficiency that prevents the breakdown of bilirubin, a substance formed from the destruction of red blood cells. While there are just a few hundred known cases worldwide, children with the condition must undergo daily 12-hour periods of exposure to special lights to survive. “This is the first time this disease has been completely cured long term with a single injection in an adult animal,” says Howard Hughes investigator Brendan Lee of Baylor College of Medicine in Houston, Texas. Cellular detox The gene therapy uses a modified adenovirus to carry a lacking gene into part of the cell where detoxification occurs. While Lee doesn’t think the treatment would cure adults, he thinks it holds promise for long-term alleviation of toxic symptoms. And the treatment could be repeated as needed. Furthermore, the approach could be used for other gene therapies targeted at similar areas of the cell. “This approach would be applicable to many diseases where you are trying to put something back, targeting the liver,” says Lee. Before human trials, however, Lee wants to see viral vectors developed that minimize the body’s immune response immediately after injection. “Fifteen years ago, the goal was to get some correction of the problem,” says Lee. “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.” The research is reported in the Proceedings of the National Academy of Sciences (read abstract).