Combination Gene and Stem Cell Therapy Cures Muscular Dystrophy in Mouse Model

They then employed a gene therapy approach based on the "Sleeping Beauty Transposon" to incorporate the gene for the protein utrophin into the stem cells. Utrophin can substitute for the defective protein dystrophin, which characterizes DMD, without generating an autoimmune response.

The last step was to treat the modified pluripotent cells with the muscle stem cell protein Pax3 (paired box 3), which induced the stem cells to differentiate into muscle cells. Pax3 is expressed in early embryonic growth where it helps to demarcate the paraxial mesoderm. In that way, PAX3 contributes to early striated muscle development since all myoblasts are derived from the paraxial mesoderm.

The modified stem cells were injected into DMD mice. Results published in the March 5, 2013, online edition of the journal Nature Communications revealed that the stem cells were incorporated into muscle tissue that displayed large numbers of micro-utrophin-positive myofibers, with biochemically restored dystrophin–glycoprotein complexes, and improved contractile strength.

"Developing methods to genetically repair muscular dystrophy in human cells, and demonstrating efficacy of muscle derived from these cells are critical near-term milestones, both for the field and for our laboratory," said senior author Dr. Rita Perlingeiro, associate professor of medicine at the University of Minnesota. "Testing in animal models is essential to developing effective technologies, but we remained focused on bringing these technologies into use in human cells and setting the stage for trials in human patients."

"We were pleased to find the newly formed myofibers expressed the markers of the correction, including utrophin," said, Dr. Perlingeiro. "However, a very important question following transplantation is if these corrected cells would self-renew, and produce new muscle stem cells in addition to the new muscle fibers."

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