Any door-to-door salesperson knows that the key to success is getting the customer to just open up. Now, gene therapists hoping to cure muscular dystrophy have found the same thing: Getting blood vessels to open up is the secret to delivering a therapeutic gene to muscle tissue. The result shows for the first time that genes injected into the bloodstream can be incorporated into a specific tissue type all over the body.
The most common form of muscular dystrophy, Duchenne muscular dystrophy, is caused by a mutant protein called dystrophin. The protein smites every muscle in the body--including skeletal muscle, the heart, and the diaphragm, which controls breathing--and the disease usually kills its victims in their 20s. Researchers have been trying to replace the gene for dystrophin for more than a decade. Although they've engineered a common-cold virus to carry a corrected version of the dystrophin gene, researchers have had difficulty delivering the fix to every muscle.
To see if leaky capillaries might help, molecular geneticist Jeffrey Chamberlain and colleagues at the University of Washington, Seattle, first injected healthy mice with a test virus containing a protein that turns tissue blue, along with a compound called VEGF that causes blood vessels to grow and makes them leaky in the process. The more VEGF they used, the bluer the mice's muscles became, indicating higher levels of the virus. Nonmuscle organs took up the virus, but did not make the color-transforming protein. Encouraged, the team injected VEGF and the virus containing a functional copy of the dystrophin gene into mice lacking the gene. Eight weeks later, most of the muscles contained proper dystrophin, and the supplemented muscles resisted injury better. Just one injection could restore normal levels of dystrophin and prevent muscles from breaking down, the team reports online 25 July in Nature Medicine.The result is "fantastic" and a "major step forward" for gene therapy, says gene therapist Savio Woo of Mount Sinai School of Medicine in New York City. And the research has made a convert of neurobiologist Beverly Davidson of the University of Iowa, Iowa City, who says she'd become skeptical that delivery to every muscle could be accomplished. "He proved me wrong," she says, but cautions that "the big hurdle will be how to translate that to a human patient."