Six weeks after muscular injection with the virus containing the muscle-restricted gene, mice exhibited high levels of the enzyme and reduced glycogen content in the injected muscle. The mice also had a reduced immune response to the new enzyme, compared to those in which gene expression was not limited to muscle, they found.
Moreover, intravenous administration of the muscle-targeted gene reduced the glycogen content of heart and skeletal muscle and corrected individual muscle fibers. The effect persisted for 24 weeks post-injection, the team reported.
A second gene therapy strategy, in which the enzyme involved in Pompe disease is inserted into the liver, is also under investigation at Duke, said Koeberl. In the January 2005 issue of Molecular Therapy, the researchers reported that the liver-targeted method also corrected symptoms of Pompe disease in mice.
"The muscle-targeted gene therapy method could circumvent the complications of neutralizing antibodies against introduced enzyme, which currently present obstacles to enzyme replacement therapy and liver-targeted gene therapy in Pompe disease," Koeberl said.
Clinical trials of either the muscle- or liver-targeted gene therapies will likely take several years to launch, Koeberl said.
Collaborators on the gene therapy studies include Baodong Sun, Haoyue Zhang, Luis Franco, Andrew Bird, Ayn Schneider, Sarah Young, Y.T. Chen, and Andy Amalfitano, all of Duke Medical Center, and Talmage Brown, of North Carolina State University College of Veterinary Medicine.