Credit: Dongsheng Duan

If we were more like mice, we'd probably be a whole lot healthier. Over the past few years, scientists have used gene therapy to treat mice for almost every condition imaginable. Unfortunately, attempts to translate such results into clinical therapy have had limited success, in part because humans are so much larger than mice. Now, Dongsheng Duan (University of Missouri, Columbia) and colleagues have found a way to administer whole-body gene therapy to dogs, suggesting that similar methods may one day be feasible in other large animals such as humans.

Duan's lab investigates Duchenne's muscular dystrophy, a fatal condition caused by mutations in the gene encoding dystrophin. Patients begin to lose motor ability during early childhood, and most die before age 30. Because all muscles in the body are affected by Duchenne's, gene therapy for such a disease would require whole-body systemic transduction. Recent studies have shown that such treatment is possible in mice, but attempts to use similar techniques in adult dogs have thus far been unsuccessful because of dogs' strong cellular immune response.

The researchers used two approaches to carry out gene transfer in beagles and in beagle–golden retriever mixes. First, they injected young adult dogs intravenously with a viral vector that had not previously been used in dogs (adeno-associated viral vector serotype 9). The vector, which carried a reporter gene but no therapeutic components, triggered an immune response and yielded limited transduction. The researchers then attempted the same technique in newborn puppies whose immune systems were not yet developed. In this case, skeletal muscle transduction was completely effective and was maintained for 6 months (Mol. Ther. published online 30 September 2008; doi:10.1038/mt.2008.207). In dogs, the transduction qualities of the viral vector were completely different from those previously observed in mice, emphasizing the difficulty in extrapolating results from one species to another.

The team's research shows that administering gene therapy to neonates has a clear immunological advantage, but there may also be a clinical advantage to treatment at a young age. New techniques have been developed to diagnose diseases such as Duchenne's in newborns. If babies can be treated for these conditions before symptoms occur, there is a possibility of avoiding clinical damage altogether.

It remains to be determined whether such gene therapy would be effective in humans. But the research of Duan and colleagues may have brought us one step closer to doing so.