(HealthDay is the new name for HealthScoutNews.)
THURSDAY, July 10, 2003 (HealthDayNews) -- Italian scientists report a possible solution to a major problem plaguing researchers working on gene therapy for muscular dystrophy: how to get the right gene to the right place to stop the muscle-wasting process that cripples people with the condition.
A newly discovered kind of stem cell has successfully carried a corrective gene to muscles in mice with one form of muscular dystrophy, says a report in the July 11 issue of Science. The researchers are based at the Stem Cell Research Institute in Milan and the Institute of Cell Biology and Tissue Engineering in Rome.
It's much too early to think about human trials, says Sharon Hesterlee, director of research and development at the Muscular Dystrophy Association, but "this is a really significant piece of work. It's the first time we've been able to do a stem cell transplant and see an actual increase in function."
The researchers used a kind of cell they discovered only last year and have named mesoangioblasts. These cells are found in blood vessel walls and are stem cells, meaning they can transform themselves into a variety of other cell types -- blood, bone, muscle and connective tissue. Most important, the Italians have found, they can migrate into muscle cells around blood vessels, carrying genes with them.
In the newly reported experiments, the gene for alpha sarcoglycan, a protein whose mutation or absence causes a form of muscular dystrophy, was inserted into mesoangioblasts, which were then grown in cell cultures. The engineered cells were injected into the arteries of mice lacking the gene.
Three months later, the researchers found active alpha sarcoglycan proteins in the muscles of the treated mice, downstream from the injection site. The treated muscles contained a large number of apparently normal fibers, and the mice were able to walk on a rotating wheel longer than untreated animals -- although not as long as healthy mice.
"I'm convinced that this is an important result, but this is still not the therapy, for mice or for patients," says a statement by research leader Dr. Giulio Cossu.
For one thing, the mesoangioblasts used in the study were taken from fetal mice, which might cause serious problems for researchers in the United States, where strict limits have been put on fetal stem cell research.
The goal of the researchers is to extract mesoangioblasts from muscular dystrophy patients and inject them back into the same patients after the addition of the needed gene, avoiding an attack on the cells by the immune system.
Different genes would have to be used for the many varieties of muscular dystrophy, but Hesterlee sees no major problem. "We have lots of experience with many forms of muscular dystrophy already, with good mouse models," she says. But until now, efforts to implant the corrective genes using other cells or viruses have been disappointing, she adds.
An American laboratory made an important contribution to the research. "Our laboratory contributed the mice, reagents and technical advice," says Kevin P. Campbell, a professor of physiology and biostatistics at the University of Iowa College of Medicine. "They needed a well-characterized animal model of muscular dystrophy, and we have a very good model."
The Iowa laboratory now has replicated the Italian experiment and will continue to do work on the subject, Campbell says.
Decisions on what to do next can't be made until all researchers doing work on muscle regeneration get together, Hesterlee says. "We have a meeting of researchers in the next two weeks, and they will plan strategy," she says.
More information
You can get an overview of muscular dystrophy from the National Institute of Neurological Diseases and Stroke or the Muscular Dystrophy Association.
