Children’s Hospital Oakland Research Institute

CHORI_SectionDr. Julie Saba.

Duchenne is characterized by muscle degeneration resulting in progressive weakness and, ultimately, heart and respiratory failure. Muscle stem cells called satellite cells can foster the regeneration of diseased muscle in DMD, but studies show that satellite cell populations become exhausted over time. In addition, satellite cell infusions have the potential to cure DMD by introducing a normal dystrophin gene into DMD muscles through remodeling. However, satellite cell treatments have been hampered by low stem cell survival and poor efficiency of incorporation into muscle. In our laboratory, we are exploring ways to expand the body’s satellite cells and to improve the survival of infused satellite cells. Specifically, our laboratory studies a natural lipid molecule called sphingosine-1-phosphate (S1P). S1P is a bioactive lipid found in the bloodstream that stimulates the proliferation of satellite cells. We find that S1P is depleted in mice exhibiting a form of DMD, which suggests that DMD may represent a state of S1P deficiency. We are using a nontoxic compound that inhibits the breakdown of S1P in order to boost S1P levels and thereby expand satellite cell pools available for muscle regeneration. In mice with a DMD-like disease, boosting S1P in this manner has led to improved satellite cell recruitment and better muscle regeneration after injury.