US FDA Grants Expanded Approval of ELEVIDYS Gene Therapy for DMD Patients Ages 4 and Above

Scientists Bullish on Stem Cells for Muscle Repair

Two MDA-supported groups have recently made great strides in stem cell therapies for muscle disease

Stem cells treat MD in dogs

MDA grantee Giulio Cossu, director of the Stem Cell Research Institute of the San Raffaele Scientific Institute of Milan (Italy), was part of an Italian and French research team that restored mobility to two dogs and stabilized function in a third, using stem cells taken from muscle blood vessels.

Maurilio Sampaolesi, at the San Raffaele Scientific Institute in Milan and the Institute of Myology at the University of Pavia (Italy), and colleagues, isolated mesoangioblasts from canine muscle biopsy samples and administered them through an artery into 10 dogs with a disorder resembling human Duchenne muscular dystrophy (DMD).

The results, published online Nov. 15 in Nature, received national media attention because the technique was effective in a large animal. This success is considered a major step toward testing these cells in humans.

Four of the dogs received their own mesoangioblasts, with an added, functional gene for the protein dystrophin, which is missing in DMD. Six other dogs received normal mesoangioblasts from a healthy donor animal, and three dogs weren't treated at all.

The dogs that received donor cells responded the best, with one of that group walking well at 13 months. (Most dogs with the disease have difficulty walking by 8 months of age and die when they're about a year old.)

The dogs were injected three to five times with 50 million cells at one-month intervals. Some of the animals were also treated with drugs to suppress the immune system's potential rejection of the new cells.

Results were documented biochemically and through at least two measures of muscle function. There was no evidence of immune response in any of the dogs.

The study's authors write that "the work reported here sets the logical premise for the start of clinical experimentation that may lead to an efficacious therapy for Duchenne muscular dystrophy," also noting that any immune system suppression needed "might be modest and perhaps transient."

Two stem cell types may be better than one

Researchers in the laboratory of MDA grantee Emanuela Gussoni at Children's Hospital in Boston have identified two proteins that counter each other's actions to regulate the balance between muscle stem cells and mature muscle fibers. They say further experiments may improve the success of muscle cell transplant strategies.

Natasha Frank at Children's, and colleagues, who published their results online Oct. 2 in the Journal of Cell Biology, say bone morphogenetic protein 4 (BMP4) keeps muscle stem cells from maturing and encourages them to continue to proliferate, while another protein, gremlin, coaxes them to mature and stop proliferating.

BMP4 is secreted at high levels by the "side population" of muscle cells that Gussoni and her colleagues identified several years ago as having stem-cell-like qualities. Gremlin is secreted in abundance in the main population of muscle cells, which don't have these stemlike characteristics.

"It seems that cells in skeletal muscle 'talk' to one another, and they can induce cell division or differentiation [maturation] by secreting specific factors," says Gussoni, who adds that the findings may have some implications for modifying cell transplantation approaches.

"Perhaps stem cells and more mature cells should be injected together in mouse models to see whether engraftment can be improved," she notes. "Perhaps the stem cells give support to other cells and may help them function better in muscle repair."

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