BioWorld International Correspondent

PARIS - Transgene SA and Mirus Corp. reported the first successful application of Mirus' gene transfer technology for the delivery of a plasmid-based vector into skeletal muscles in animal models of Duchenne's disease, a form of muscular dystrophy.

Strasbourg-based Transgene said it achieved "efficient delivery" of its gene vector into at least 10 percent of large-limb muscles in primate and nonprimate animal models of the fatal genetic disease.

That represents the first milestone under the five-year research and licensing agreement the two companies signed in October 2000 covering the development of gene therapy products using Mirus' gene transfer technology in conjunction with Transgene's plasmid-based vector. The achievement also triggered an initial milestone payment from Transgene to Mirus, of Madison, Wis., since Transgene is financing the research program.

The deal gives the French company access to the high-pressure, intra-arterial delivery system developed by Mirus, which ensures an efficient transfer of vectors from the bloodstream into muscles, enabling the therapeutic gene to be delivered throughout the muscle mass. It overcomes the cell transfection limitations of the traditional form of administration directly into the muscle tissue, which delivers the genes only to the area around the point of injection.

The research agreement provided for Transgene to apply Mirus' technology in both Duchenne's disease and multiple sclerosis and gave the French company the option of licensing the technology for developing gene therapy products for those two pathologies and five other target pathologies to be selected during the term of the deal.

Since then, however, Transgene has refocused its gene therapy development on two pathologies - cancer and muscular dystrophy - and dropped multiple sclerosis. The company already has exercised its option to license the Mirus technology for Duchenne's, obtaining exclusive worldwide rights in muscular dystrophy, its vice president of research, Serge Braun, told BioWorld International. Braun added that the option of selecting five other pathologies remained open, with one possible area being other genetic muscular diseases.

Transgene's gene therapy for muscular dystrophy, which consists of a nonviral vector encoding dystrophin, is nearing the end of a two-year Phase I trial at the Institute of Myology in the La Pitié-Salp trière hospital in Paris. That program is being financed by the French muscular dystrophy association, but its funding does not encompass the separate, but related, research program that Transgene is conducting in conjunction with Mirus.

Braun stressed that the clinical trial was testing the tolerability of the therapy, not its efficacy, because "with the existing vector, we could not expect to have a significant therapeutic effect. We had to improve the vector's efficacy."

That has now happened, but even after the therapy has been adapted to incorporate the Mirus delivery method for use in humans, the next clinical trial still will test only its tolerability, Braun said.

That said, Transgene is confident that its investment in Mirus' technology will pay off. "The possibility of efficiently delivering therapeutic genes through large masses of skeletal tissues is an encouraging prospect for our candidate dystrophin plasmid for the treatment of Duchenne's muscular dystrophy," said CEO Jean-François Carmier. Acknowledging that the "low efficiency of cell transfection" of plasmid vectors was a "major obstacle," he described the successful application of the Mirus delivery system as a "breakthrough in the administration" of those vectors.