Autologous cell-based therapies for Duchenne muscular dystrophy is under investigation
Researchers at the University of Minnesota’s Lillehei Heart Institute are about to discover a cure for Duchenne muscular dystrophy with the use of stem cells. The results of serial experiments on rats conducted so far are promising and it is likely that in the future this debilitating, lethal, muscle disease be cured.
First, scientists have turned skin cells into pluripotent cells, that is cells that can differentiate into any cell in the body. Researchers create pluripotent cells from the skin of rats carrying mutations in the dystrophin and utrophin gene to create a model as close to Duchenne muscular dystrophy in humans. The resulting disease in rats practically mimicked muscle dystrophy in humans. The next step was to send a gene called “micro-utrophin” to the pluripotent cells that the researchers intend to differentiate. They have done this with ‘Sleeping Beauty transposon’, which is a tool for genetic correction, which means it can introduce certain genes in the human genome.
These two components, dystrophin and utrophin, are similar in many ways because both have a role in supporting muscle fibers and in muscle force generation. In Duchenne muscular dystrophy, which is a genetic disease, dystrophin is absent so the body gradually becomes weaker as the muscles begin to atrophy. Because it is a genetic disorder characterized by a mutation in the dystrophin gene, Duchenne muscular dystrophy is incurable and treatment is only supportive. However, the researchers found that utrophin is active and functional in these patients and that can take dystrophin function.
The next experiment was conducted by Rita Perlingeiro, Ph.D. who generated skeletal muscle stem cells from pluripotent cells. The experiment consisted in stimulating muscle cells to become pluripotent cells with a protein called Pax3. The Pax3-induced muscle stem cells were then transplanted into the same rats from which were taken the pluripotent stem cells. In this way they were created muscle-generating stem cells without the body to trigger an immune reaction.
Perlingeiro, the Lillehei Endowed Scholar within the Lillehei Heart Institute and an associate professor in the University of Minnesota Medical School, said she is excited to see that the newly formed myofibers expressed correction biomarkers including utrophin. She added that it is very interesting to find out if these cells, after transplantation, would self-renew and would give rise to new muscle stem cells in addition to the new muscle fibers. Antonio Filareto, Ph.D., a postdoctoral fellow in Perlingeiro’s laboratory and the lead author on the study, said: “Utilizing corrected induced pluripotent stem cells to target this specific genetic disease proved effective in restoring function.”