University of Minnesota researchers, using stem cell technology, have sparked muscle regeneration in laboratory mice with a fast-moving form of muscular dystrophy, a disease that severely weakens muscles.
They hope their breakthrough in mice will one day lead to more effective treatments for humans who have the disease known as Duchenne Muscular Dystrophy.
Symptoms of the fatal degenerative disorder, which mostly affects boys, usually occur before age six. They include muscle weakness, difficulty walking, fatigue and learning disabilities. Death typically happens by age 25, most often due to breathing issues. The university's animal study combined three technologies to essentially "correct" the gene mutation that causes Duchenne Muscular Dystrophy.
First, researchers took skin cells from the tail of a mouse with the muscular disease and reprogrammed the cells so they could make any tissue in the animal's body.
"[The cells] forget that they're skin," said principle investigator Rita Perlingeiro, an associate professor in the University of Minnesota Medical School.
The next step was to correct the disease still present in the reprogrammed cells. Perlingeiro's team used a virus to insert a missing gene that provides muscle strength into the cells. The gene was tagged with a fluorescent protein so researchers could isolate the corrected cells and give them new instructions.
Finally, the new cells were reprogrammed again, this time to become muscle stem cells. They were then transplanted back into the sick mice.
"What we saw is that those cells were able to engraft, they were present, they made myofibers in the muscles of these mice," said Perlingeiro. "They also generate stem cells that would sit in the muscle and respond to injury when necessary."
While the results appear promising to the researchers, Perlingeiro's team did not cure the mice, which were very sick by the time they received the therapy.
"They live a shorter life compared to others because of this mutation," says Perlingeiro. "But even in this environment, that was very sick, you were able to see that the cells were able to restore some function."
University researchers acknowledge there are many challenges ahead as they try to adapt their techniques to potential clinical studies in humans. One significant challenge will be finding a way to insert missing genes into reprogrammed cells without using potentially dangerous viruses.
"We have lots and lots of obstacles in front of us," said Perlingeiro. "But I think what I can say is that this study really shows us proof of principle — that you can use all of these strategies together, and we can come up with strategies to correct the disease and make muscle. These three steps, we know, we can accomplish now."
The University of Minnesota study is published in the journal Nature Communications. It was funded with grants from the National Institutes of Health, the Muscular Dystrophy Centre Core Laboratories, the Dr. Bob and Jean Smith Foundation and the Greg Marzolf Jr. Foundation.