Parvanovová P1,2, Evinová A2, Tučanová Koprušáková M3, Kolísek M2

1Institute of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava

2Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava

3Clinics of Neurology, University Hospital in Martin, Comenius University in Bratislavav

 

Miyoshi myopathy is a subtype of dysferlinopathy characterized by muscle weakness and atrophy, mainly in the distal parts of the legs. Dysferlinopathies are caused by mutations in the DYSF gene, and patients may have proximal or distal myopathy. The first symptoms usually appear in young adulthood (average age of onset is 20 years) and include weakness and atrophy of the calves, which in some cases may be asymmetrical, leading to an inability to jump, run, or tiptoe. Over the years, weakness and atrophy usually extend to the thighs and gluteal muscles. The forearms may be mildly atrophic with a decrease in grip strength. Despite tremendous efforts, there is no effective treatment for this disease at present.

Current research is turning its attention to the study of the mitochondria, whose function is to obtain energy through cellular respiration. In our work, we focused on the study of mitochondrial respiration in leukocytes from Miyoshi patients. Peripheral blood was used as a starting specimen. Subsequently, leukocytes were isolated by using a commercially available LeucoSep kit. An O2k respirometer (Oroboros) was used to measure respiration. The standard CCP protocol (Coupling-Control Protocol) was used for the measurement. The first measurement was performed on the patients at the time of diagnosis. As part of the treatment, the patients were given magnesium (Mg) at an effective dose of 400 mg in the form of Mg-citrate (Diasporal 400 Extra, Protina Pharm. GmbH.). Magnesium was administered to the patients (based on empirical findings) for the duration of one month, and the patients' blood was again collected, and the leukocytes were examined for the parameters of respiration. Currently, the role of Mg in neuromuscular diseases is still not fully understood. However, previous findings suggested reduced Mg levels in intramuscular diseases.  It is not yet clear whether these differences result from the different sarcolemmal permeability, the role of Mg in cellular energetics, increased oxidative stress, or the pro-inflammatory effect of Mg deficiency, among other factors.

We conclude that, Mg supplementation (400 mg Mg per day) after undergoing 30 days long supplementation regiment improves parameters of mitochondrial respiration in leukocytes of Miyoshi dysferlinopathy patients.

Acknowledgements

This work was supported by the project GUK 284/2022 and APVV-19-0222