Antibiotics Against a Genetic Disorder?

Some antibiotics have more going for them than their power to kill bacteria. Mice studies published in the August Journal of Clinical Investigation show that some of these drugs may also be used to treat Duchenne muscular dystrophy, a genetic disease in which victims become paralyzed by progressively weak muscles and usually die in their teens or early 20s.

A class of antibiotics called aminoglycosides quell infection by tightly binding to the ribosomes--cellular factories that translate RNA into proteins--of invading bacteria, thus shutting them down. The same compounds also latch onto the slightly different ribosomes in animal cells, but not as tightly. As a result, the host's protein assembly line becomes somewhat sloppy: Occasionally, the wrong amino acid is inserted into a growing protein. The same imprecision can make a ribosome ignore so-called stop codons. These nucleotide sequences normally appear at the end of a gene, where they act like flags, alerting the ribosome that the protein under construction is finished. When a mutation produces a stop codon in the wrong place, it can lead to truncated, and thus worthless, protein. Aminoglycosides thus can trick the ribosome into ignoring the stop sign, allowing it to make the full-length protein.

Researchers have seized on this as a possible way to treat Duchenne, in which a truncated version of a protein called dystrophin weakens skeletal muscles. When a team led by physiologist Lee Sweeney of the University of Pennsylvania in Philadelphia gave the aminoglycoside gentamicin to two groups of mice with a disease similar to Duchenne for 2 weeks, the animals showed fewer signs of impairment than a control group, and their blood levels of creatine kinase, an enzyme that leaks out of damaged muscles, were 60% lower. Their muscles--after being removed--didn't tear as easily and contained more dystrophin.

Gentamicin can cause serious side effects like hearing loss or kidney damage, but Sweeney hopes that low doses may prove effective and safe, and he is planning small-scale clinical trials. Eventually, says microbiologist David Bedwell of the University of Alabama at Birmingham, gene therapy may simply replace the faulty gene in Duchenne patients' muscles. But in the meantime, he says, a drug regimen "may improve the quality of life and the life expectancy for these patients."