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| Item Type: | Article |
|---|---|
| Title: | 4-phenylbutyrate restores localization and membrane repair to human dysferlin mutations |
| Creators Name: | Tominaga, K., Tominaga, N., Williams, E.O., Rufibach, L., Schöwel, V., Spuler, S., Viswanathan, M. and Guarente, L.P. |
| Abstract: | 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. |
| Keywords: | Musculoskeletal Medicine, Drugs, Animals, Mice |
| Source: | iScience |
| ISSN: | 2589-0042 |
| Publisher: | Cell Press |
| Volume: | 25 |
| Number: | 1 |
| Page Range: | 103667 |
| Date: | 21 January 2022 |
| Official Publication: | https://doi.org/10.1016/j.isci.2021.103667 |
| PubMed: | View item in PubMed |
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