| First Author | Nogami K | Year | 2021 |
| Journal | Hum Mol Genet | Volume | 30 |
| Issue | 11 | Pages | 1006-1019 |
| PubMed ID | 33822956 | Mgi Jnum | J:312033 |
| Mgi Id | MGI:6715053 | Doi | 10.1093/hmg/ddab100 |
| Citation | Nogami K, et al. (2021) Pharmacological activation of SERCA ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice. Hum Mol Genet 30(11):1006-1019 |
| abstractText | Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscular weakness because of the loss of dystrophin. Extracellular Ca2+ flows into the cytoplasm through membrane tears in dystrophin-deficient myofibers, which leads to muscle contracture and necrosis. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) takes up cytosolic Ca2+ into the sarcoplasmic reticulum, but its activity is decreased in dystrophic muscle. Here, we show that an allosteric SERCA activator, CDN1163, ameliorates dystrophic phenotypes in dystrophin-deficient mdx mice. The administration of CDN1163 prevented exercise-induced muscular damage and restored mitochondrial function. In addition, treatment with CDN1163 for 7 weeks enhanced muscular strength and reduced muscular degeneration and fibrosis in mdx mice. Our findings provide preclinical proof-of-concept evidence that pharmacological activation of SERCA could be a promising therapeutic strategy for DMD. Moreover, CDN1163 improved muscular strength surprisingly in wild-type mice, which may pave the new way for the treatment of muscular dysfunction. |
