Preclinical research into taurine as a DMD treatment identifies new biomarkers to track muscle degeneration and oxidative stress
Taurine is a variety of amino acid that supports cellular and immune health, as well as nervous system function. While dietary intake of taurine is usually sufficient, taurine supplements have been shown to improve health in people with chronic diseases.
Study to explore its potential as a DMD treatment
In 2018, Duchenne UK funded a research project to explore the value of taurine supplements as a treatment for Duchenne muscular dystrophy (DMD).
Taurine has the potential to be successfully used clinically as it’s inexpensive, can be taken orally, and is safe.
The project, led Dr Jessica Terrill at the University of Western Australia (UWA) in Perth, in collaboration with researchers at the University of Nantes in France, sought to discover if taurine prevented muscle damage in the DMD animal model.
Specifically, the researchers wanted to see if taurine could help protect muscles by reducing muscle degeneration caused by necrosis (muscle cell death).
Commencing in 2018, the research had two aims:
- To test the effectiveness of taurine in a rat model of dystrophy. Previous work had shown that taurine was effective in the mouse model of dystrophy. The rat model was chosen for this research because dystropathology was more severe than in the mouse model, thus more closely resembling the human disease.
- To identify molecules in blood or urine that provide information about the degree of necrosis in muscle. Such molecules are described as biomarkers because they can be used to indirectly assess the severity of dystropathology.
What the research found
The research has now completed, and it was successful in identifying a blood biomarker to track necrosis in the muscle. The researchers observed increased oxidative stress (a toxic cellular state) and increased necrosis in the dystrophic rat muscles and then identified a blood biomarker of oxidative stress (oxidised albumin). The research team showed oxidised albumin was elevated in the blood of dystrophic rats with high degree of necrosis in the muscles.
The researchers also tested blood from non-ambulatory DMD adults and found that oxidised albumin was also elevated. In future, this oxidative stress biomarker may be useful in showing how the disease is progressing or whether a treatment is effective in slowing or preventing dystropathology.
What the research wasn’t able to demonstrate
Taurine was not found to be effective in preventing muscle damage in the rat model of muscular dystrophy. The reason for the lack of effectiveness may relate to the levels of taurine in the muscles of the dystrophic rat, which were already unexpectedly high.
This contradicts what was observed in the dystrophic mouse model, where there was a deficiency of taurine and taurine treatment has been shown to be effective.
An important question remains as to whether there is a deficiency of taurine in dystrophic muscles of humans, suggesting taurine treatment may be beneficial. To answer this question, the researchers would need to measure taurine in muscle biopsies.
Terrill, J. R., C. Huchet, C. Le Guiner, A. Lafoux, D. Caudal, A. Tulangekar, R. J. Bryson-Richardson, T. E. Sztal, M. D. Grounds and P. G. Arthur (2023). Muscle Pathology in Dystrophic Rats and Zebrafish Is Unresponsive to Taurine Treatment, Compared to the mdx Mouse Model for Duchenne Muscular Dystrophy. Metabolites 13(2): 232.
Iwasaki, T., J. R. Terrill, K. Kawarai, Y. Miyata, T. Tagami, N. Maeda, Y. Hasegawa, T. Watanabe, M. D. Grounds and P. G. Arthur (2022). The location of protein oxidation in dystrophic skeletal muscle from the mdx mouse model of Duchenne muscular dystrophy. Acta Histochem 124(8): 151959.
Al-Mshhdani, B. A., M. D. Grounds, P. G. Arthur and J. R. Terrill (2021). A Blood Biomarker for Duchenne Muscular Dystrophy Shows That Oxidation State of Albumin Correlates with Protein Oxidation and Damage in Mdx Muscle. Antioxidants (Basel) 10(8).
Terrill, J. R., B. A. Al-Mshhdani, M. N. Duong, C. D. Wingate, Z. Abbas, A. P. Baustista, A. K. Bettis, C. J. Balog-Alvarez, J. N. Kornegay, P. P. Nghiem, M. D. Grounds and P. G. Arthur (2020). Oxidative damage to urinary proteins from the GRMD dog and mdx mouse as biomarkers of dystropathology in Duchenne muscular dystrophy. PLoS One 15(10): e0240317.
Grounds, M. D., J. R. Terrill, B. A. Al-Mshhdani, M. N. Duong, H. G. Radley-Crabb and P. G. Arthur (2020). Biomarkers for Duchenne muscular dystrophy: myonecrosis, inflammation and oxidative stress. Dis Model Mech 13(2).
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