Mitochondrial health as therapeutic target for Duchenne muscular dystrophy: studies in taurine-treated mdx mice

Dhuyvetter Hanne, 2023
1. Summary Background: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive disorder, characterized by progressive muscle degeneration and lowered life expectancy (30-40 years) due to mutations in the DMD gene. Impaired mitophagy has been discovered to be a major contributor to the disease progression, becoming the therapeutic target in this investigation. The golden standard for treatment these days is glucocorticoids, which come with unfavorable adverse effects, leading to the need for more research. In this thesis, taurine as a supportive therapy is studied, and more specifically its effect on mitochondrial health as this osmolyte has promising anti-inflammatory, antioxidant, and cytoprotective effects. Methods: Four- to eight-week-old mice are used throughout this study, which consisted of two different analyses, firstly a Western blotting analysis on the musculus extensor digitorum longus (EDL) on untreated MDX mice (a model for DMD) and taurine-treated MDX mice was performed. Followed by immunofluorescence staining on the musculus tibialis anterior (TIB) on BLA mice (healthy control), saline-treated MDX mice, and taurine-treated MDX mice. The mitophagy markers that were studied in both of the aforementioned techniques were LC3II, SQSTM1, and ATG7. Results: No significant results were found between MDX mice and taurine-treated MDX mice. Although there were tendencies of increased SQSTM1 levels and decreased LC3II levels. Conclusion: This study did not pick up a beneficial effect of taurine treatment on mitophagy in MDX mice, yet observed a trend of increased SQSTM1 and decreased LC3II levels in mitochondrial protein fractions from the EDL muscle. 2. Layman summary with societal impact About half of Duchenne muscular dystrophy (DMD) patients use various vitamins and nutritional supplements, but the recommendations and guidelines regarding these fall short.8 As DMD is still an incurable disease, the quest for better medicine and tools is therefore highly necessary. In this study, the focus lies on nutritional supplements, as they can have a lot of beneficial effects. Supportive therapies, especially nutritional supplements, may aid in reducing the dosage of sustained corticosteroid treatment, which still is the standard therapy but often comes with severe adverse effects8. In that logic, nutritional supplements could ameliorate the quality of life of DMD patients. Currently, there are solely two nutritional supplements that are recommended for these patients namely vitamin D and calcium. However, other supplements are being scoped and discussed in the literature. A few examples include; glutamine, L-arginine, leucine, and taurine52. This master thesis focuses on taurine, a supplement with known anti-inflammatory effects resulting in a plausible supportive therapy option to further assist these patients52. This approach highlights the impact of taurine, more specifically its effect on mitophagy. This master thesis found trends in the results of both quantitative and qualitative research, conducted by using Western blot and immunofluorescence staining, however, these results were not statistically significant. Nonetheless, this topic seems of interest to be further researched, given an optimized use of supplements in DMD.

Promotor Boel De Paepe
Opleiding Biomedische Wetenschappen
Domein Nutrition and Metabolism
Kernwoorden Duchenne muscular dystrophy mitophagy taurine