| First Author | de Zélicourt A | Year | 2022 |
| Journal | EMBO Mol Med | Volume | 14 |
| Issue | 5 | Pages | e12860 |
| PubMed ID | 35298089 | Mgi Jnum | J:327511 |
| Mgi Id | MGI:7277918 | Doi | 10.15252/emmm.202012860 |
| Citation | de Zelicourt A, et al. (2022) CD38-NADase is a new major contributor to Duchenne muscular dystrophic phenotype. EMBO Mol Med 14(5):e12860 |
| abstractText | Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration. Two important deleterious features are a Ca(2+) dysregulation linked to Ca(2+) influxes associated with ryanodine receptor hyperactivation, and a muscular nicotinamide adenine dinucleotide (NAD(+) ) deficit. Here, we identified that deletion in mdx mice of CD38, a NAD(+) glycohydrolase-producing modulators of Ca(2+) signaling, led to a fully restored heart function and structure, with skeletal muscle performance improvements, associated with a reduction in inflammation and senescence markers. Muscle NAD(+) levels were also fully restored, while the levels of the two main products of CD38, nicotinamide and ADP-ribose, were reduced, in heart, diaphragm, and limb. In cardiomyocytes from mdx/CD38(-/-) mice, the pathological spontaneous Ca(2+) activity was reduced, as well as in myotubes from DMD patients treated with isatuximab (SARCLISA((R)) ) a monoclonal anti-CD38 antibody. Finally, treatment of mdx and utrophin-dystrophin-deficient (mdx/utr(-/-) ) mice with CD38 inhibitors resulted in improved skeletal muscle performances. Thus, we demonstrate that CD38 actively contributes to DMD physiopathology. We propose that a selective anti-CD38 therapeutic intervention could be highly relevant to develop for DMD patients. |
