Novel Cell Therapy Restores Dystrophin in Mouse Model of DMD

March 20, 2018

Rare Daily Staff

Researchers report that they significantly improved muscle function in a mouse model of the rare and fatal condition Duchenne muscular dystrophy by implanting cells made by fusing a normal human muscle cell with a muscle cell from a person with the condition.

The findings are reported by researchers from the University of Illinois at Chicago in the Stem Cell Reviews and Reports.

These so-called “chimeric cells,” are made by combining a normal donor cell containing a functioning copy of the gene for dystrophin— a muscle protein lacking in people with Duchenne muscular dystrophy—with a cell from a recipient with the disease. In an earlier paper in January in Stem Cell Reviews and Reports, the researchers used mouse donor and recipient cells to make chimeric cells that boosted dystrophin levels by 37 percent and improved muscle function when implanted into the muscles of a mouse model of Duchenne muscular dystrophy. They found the new cells had both donor and recipient characteristics and interacted with their surroundings like normal cells. The chimeric cells remained viable and produced dystrophin for 30 days.

Now, the research group reported similar findings using human cells implanted in a mouse model of Duchenne muscular dystrophy.

“Our results point to the long-term survival of these cells and helps establish the use of chimeric cells as a novel promising potential therapy for patients with Duchenne muscular dystrophy,” said Maria Siemionow, professor of orthopedic surgery in the UIC College of Medicine and leader of the study.

The researchers say their treatment may hold benefits over other promising avenues being pursued to treat DMD, such as stem cell therapy and gene therapy. Stem cell therapies, which use implanted dystrophin genes, require the recipient to take immunosuppressive drugs to prevent rejection and face the threat of dangerous reactions because the cell can be viewed as foreign. Alternatively, gene therapy relies on viruses to carry copies of missing or dysfunctional genes to cells. Cells become immune to viral infection, rendering the therapy ineffective.

“This is not conventional stem cell therapy,” said Siemionow. “We are restoring dystrophin in such a way that the recipient won’t need to take anti-rejection therapy because the implanted chimeric cells can evade the recipient’s immune system. In traditional stem cell therapy, the implanted cells are 100 percent ‘other’ and anti-rejection medicine is needed to prevent the host immune system from destroying those foreign cells.”

If such cells were to be used to treat a patient with Duchenne muscular dystrophy, then normal muscle cells from the recipient’s father or close relative would be fused with muscle cells from the patient.

When the cells were implanted into the leg muscles of a mouse model of Duchenne muscular dystrophy, dystrophin levels rose approximately 20 percent of muscle fibers affected by the implanted cells at 90 days post-implantation, enough to produce a significant improvement in muscle function.

Improvements of more than 60 percent were seen in muscle function tests of the implanted mice, and improvements of more than 20 percent in tests of muscle fatigue tolerance.

Siemionow and her son Kris Siemionow, who was a co-author of the paper, recently launched Dystrogen Therapeutics, a company to develop their chimeric cells into a therapy to treat Duchenne muscular dystrophy.

March 19, 2018
Photo: Maria and Kris Siemionow (Photo by Jenny Fontaine)


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