How Mosaics May Help Cure Muscular Dystrophy—Researchers Find the Genome Editing May Cure DMD

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With the progression of modern genomic studies and technological advancements in biomedical engineering, a future wherein genetic disorders are cured after birth is not far off. However, for those lucky mice born in today's labs, scientists can cure them of such illnesses even before birth.

Looking into the genetic causes of the heritable X-linked disease Duchenne Muscular Dystrophy (DMD), researchers at the University of Texas Southwestern Medical Center found that the primary symptoms caused by the genetic anomalies could be cured with a genomic editing tool, that changes the makeup of the mice even before sperm reaches an egg.

Publishing their results last Friday, Sept. 5, in the journal Science, the researchers were able to not only gain a better understanding of how the disease came to be, but also were able to correct the genomes of many mice, creating mosaic-like mice with a wide range of results.

"Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, a protein required for muscle fiber integrity" lead researcher Chengzu Long said. "DMD is characterized by progressive muscle weakness and a shortened life span, and [as of yet] there is no effective treatment."

However, their results point towards a brighter future in research of humans who are afflicted by Duchenne Muscular Dystrophy. As an X-linked genetic disorder, DMD primarily affects males, while females can either be affected by the disorder or live normally as carriers who can pass DMD onto their offspring later in life. Serious in its affect on the development and maintenance of all major muscle groups, DMD usually presents itself in early childhood at the ages between 3 and 5, but by early teens can be fatal, as atrophy affects the heart and respiratory muscles. While the disorder is relatively rare, major advancements in the field of genomics have allowed for cross-over to help find solutions to problems like DMD, which were not the original goals of the new technology.

Long and his fellow researchers hypothesized that by using genome editing they could correct the dystrophin encoding gene (Dmd), and through mutations of the germ line, correct an entire generation of mice with a few simple changes snipped here and there. Monitoring the lives of the mice from fertilization to death, the researchers were able to find that their genome editing gave rise to what they call "mosaic mice", composed of a mosaic of fixed cells and mutated dysfunctional ones as well. Overall, the few cells changed in the lab, led the mice to live longer, healthier lives with fractions of the symptoms and stronger muscle integrity.

"Genome editing produced genetically mosaic animals containing 2 to 100% correction of the Dmd gene" Long said. "The degree of muscle phenotypic rescue in mosaic mice exceeded the efficiency of gene correction, likely reflecting an advantage of the corrected cells and their contribution to regenerating muscle."

While the research is mostly applicable to in vitro fertilization at the moment, where genomic researchers could fix the disorder prior to implantation of an embryo, the team is hopeful that continuing advancements will allow for treatment of DMD in patients whose symptoms arise after birth. Though this experiment has proven itself effective as a preventative measure, continued research will be vital in the development of effective treatments and perhaps cures for the myriad of forms of muscular dystrophy.

Long says that "with anticipated technological advances that will facilitate genome editing of postnatal somatic cells, this strategy may one day allow correction of disease-causing mutations in the muscle tissue of patients with DMD."