| First Author | Tominaga K | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 1 | Pages | 103667 |
| PubMed ID | 35028538 | Mgi Jnum | J:321430 |
| Mgi Id | MGI:6854219 | Doi | 10.1016/j.isci.2021.103667 |
| Citation | Tominaga K, et al. (2022) 4-Phenylbutyrate restores localization and membrane repair to human dysferlin mutations. iScience 25(1):103667 |
| abstractText | Dysferlinopathies are muscular dystrophies caused by recessive loss-of-function mutations in dysferlin (DYSF), a membrane protein involved in skeletal muscle membrane repair. We describe a cell-based assay in which human DYSF proteins bearing missense mutations are quantitatively assayed for membrane localization by flow cytometry and identified 64 localization-defective DYSF mutations. Using this platform, we show that the clinically approved drug 4-phenylbutryric acid (4-PBA) partially restores membrane localization to 25 mutations, as well as membrane repair to cultured myotubes expressing 2 different mutations. Two-day oral administration of 4-PBA to mice homozygous for one of these mutations restored myofiber membrane repair. 4-PBA may hold therapeutic potential for treating a subset of humans with muscular dystrophy due to dysferlin deficiency. |
