Febuxostat ameliorates muscle degeneration and movement disorder of the dystrophin mutant model in Caenorhabditis elegans

The Journal of Physiological Sciences - Tập 73 - Trang 1-9 - 2023
Sawako Yoshina1, Luna Izuhara1, Rei Mashima1,2, Yuka Maejima2, Naoyuki Kamatani1,3, Shohei Mitani1
1Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
2Tokyo Women’s Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, Japan
3Stagen. Co. Ltd., 4-11-6, Kuramae, Taito-Ku, Tokyo 111-0051, Japan

Tóm tắt

Duchenne muscular dystrophy (DMD) is an inherited disorder with mutations in the dystrophin gene characterized by progressive muscle degeneration and weakness. Therapy such as administration of glucocorticoids, exon skipping of mutant genes and introduction of dystrophin mini-genes have been tried, but there is no radical therapy for DMD. In this study, we used C. elegans carrying mutations in the dys-1 gene as a model of DMD to examine the effects of febuxostat (FBX). We applied FBX to dys-1 mutant animals harboring a marker for muscle nuclei and mitochondria, and found that FBX ameliorates the muscle loss. We next used a severer model dys-1; unc-22 double mutant and found the dys-1 mutation causes a weakened muscle contraction. We applied FBX and other compounds to the double mutant animals and assayed the movement. We found that the administration of FBX in combination of uric acid has the best effects on the DMD model.

Tài liệu tham khảo

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