Posted on February 26, 2001 at 11:55 a.m.
BIRMINGHAM, AL — A commonly prescribed antibiotic used to fight bacterial infections may prove effective in treating genetic diseases such as Hurler Syndrome, according to a recent study by researchers at UAB (University of Alabama at Birmingham). Details of the study appear in the February issue of Human Molecular Genetics.
Hurler Syndrome, which affects approximately one in 100,000 newborns in the United States, is a genetic disease caused most often by a stop mutation, or an interruption of a naturally occurring process in the cell. “The cells do not produce a particular enzyme essential for breaking down long chains of sugars,” says David Bedwell, Ph.D., associate professor of microbiology at UAB. “The sugar chains accumulate in the cells, causing progressive damage and eventually death, usually by age 10 or 12. It’s a devastating disease.”In laboratory studies, researchers found that cells from patients with Hurler Syndrome showed increased enzyme activity when treated with the antibiotic gentamicin. “The drug overrides the stop mutation to restore enough enzyme production — about three percent — to be effective,” says Bedwell. “In children with Hurler Syndrome, it may be a sufficient amount to allow them to live longer, more normal lives.”
The treatment also may work for other genetic diseases that result from stop mutations. “With most genetic diseases, some percentage of cases are the result of a stop mutation,” Bedwell says. “With Hurler Syndrome, stop mutations account for about 70 percent of cases; with cystic fibrosis, about 10 percent of cases. This treatment could potentially be applicable to many genetic diseases.”
The study also showed that the drug increased enzyme activity for up to two days after treatment. “Although gentamicin has been safely administered to patients for 25 years to treat bacterial infections, there are side effects from administering it on an ongoing basis,” Bedwell says. “We need to investigate further to determine if it can be administered intermittently, or if we may be able to co-administer it with other treatments to block side effects. Or, it may be that a similar compound exists that will work without the side effects.”
Although other potential therapies already exist, none of them are ideal. “Bone marrow transplants carry the risk of complications from anti-rejection drugs. Enzyme replacement therapies, which involve injecting foreign antigens, risk immune response; and gene therapy is still years away,” Bedwell says.
The next step is to test the treatment in mice. “We will make a mouse model with Hurler Syndrome to see if we can correct the stop mutation in the mouse,” Bedwell says. “We are still at least a couple of years away from clinical trails, but we are building on a large body of evidence that suggests this treatment will work.”