In Utero DMD Therapy Was Unsuccessful in Murine Models

The current standards-of-care for those with Duchenne muscular dystrophy (DMD) include corticosteroids, immunosuppressive treatments, physical therapy, and occupational therapy (among others). Gene therapy has the potential to change the treatment landscape for DMD, though gene therapy options are currently limited in scope. Because of this, some researchers have been exploring cell therapy as an option for care. This therapeutic option has been shown to halt the progression of muscular and cardiac damage. 

However, shares Rare Disease Advisor, there are some difficulties associated with cell therapy. For example, the immune cells may reject transplanted cells, causing additional health issues. Researchers have been exploring in utero cell transplants as an option; given the fact that fetal immune cells are still young and somewhat naive, there is less of a chance that the transplanted cells will be rejected. More recently, researchers sought to understand whether transplanting myoblasts and adipose-derived mesenchymal stem cells intraperitoneally and transplacentally would be beneficial for DMD.

Unpacking the Study

In their research shared in Regenerative Therapy, the study authors explored this transplantation method in murine (mice) models of Duchenne muscular dystrophy. More specifically, intraperitoneally transplanted myoblasts were given to 22 mice fetuses, intraperitoneally transplanted mesenchymal stem cells were given to 21 mice fetuses, transplacentally transplanted myoblasts were given to seven mice fetuses, and transplacentally transplanted mesenchymal stem cells were given to eight mice fetuses. 

The study found that:

  • 40.9% of mice fetuses given intraperitoneal myoblast transplantation survived; the remaining 49.1% died before birth.
  • Only 1 fetus (4.76%) given intraperitoneal mesenchymal stem cell transplant survived until birth. 
  • 100% of the mice fetuses receiving transplacental mesenchymal stem cell transplantation died. 
  • In fetuses receiving transplacental myoblasts, 85.7% survived. 

Ultimately, the study found that in utero transplantation for DMD was ineffective in mice models. However, given the fact that mice models and humans may respond differently, or different administration routes may be used, the researchers are interested in further studies within this realm. 

Duchenne Muscular Dystrophy (DMD): What It Is

Altogether, there are nine different forms of muscular dystrophy; Duchenne muscular dystrophy (DMD) is a somewhat severe form that exists under this greater umbrella. Caused by DMD variants, and inherited in an X-linked recessive pattern, this rare genetic disorder is characterized by the inability to make dystrophin (a protein) in the muscles. As a result, individuals with DMD have progressive muscle weakness; many use mobility assistance by their teenage years. DMD occurs in 1 in every 3,500 male births and 1 in every 50 million female births.

Typically, symptoms manifest before six years old. These can (but do not always) include:

  • Muscle weakness and atrophy that begins in the legs, pelvis, and thighs before progressing throughout the body
  • Fatigue
  • Motor skill difficulties
  • Shortness of breath
  • Cardiomyopathy
  • Irregular heart rhythms
  • Delayed speech and language development
  • Learning and cognitive delays
  • Frequent tripping and falling
  • Difficulty walking or moving positions
  • Heart disease (in later stages)
  • Respiratory failure (in later stages) 
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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