A study recently published in Scientific Reports revealed that skeletal muscle in a mouse model of Pompe disease had altered electrical properties, and some parameters may be useful as measures for the status, severity, and progression of the disease.

The experimental study conducted by Nagy et al compared 10 Pompe and 10 wild-type mice and noticed that while body mass remained similar in both groups, hindlimb girth and muscle mass decreased in Pompe mice at 25 and 30 weeks of age, respectively. At 30 weeks of age, the scientists obtained a dielectric measuring cell from the gastrocnemius muscle to conduct ex vivo impedance myography (EIM) studies.

The authors observed a suboptimal record for Pompe mice, reporting significantly lower longitudinal and transverse conductivities, decreased intracellular resistivity (ρintracellular) in both directions, and higher Cole-Cole complex resistivity parameters (ρo and ρo) at frequencies of 1 MHz and above.


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Interestingly, the variation in longitudinal conductivity and ρintracellular correlated with increased glycogen content in the cells of Pompe mice. On the other hand, extracellular resistivity (ρextracellular) did not showcase differences between Pompe and wild-type mice.

“We hypothesized that intracellular myofiber abnormalities associated with early stage Pompe disease would produce alterations in the electrical properties of skeletal muscle,“ the authors wrote. “Using an ex vivo EIM approach, we were able to detect significant changes in the intrinsic volume electrical conduction properties of muscle at this relatively early stage in Pompe disease progression.“

They added, “Whereas both longitudinal and transverse relative permittivity remained unchanged at all frequencies, conductivity values in both directions showed a significant reduction in the Pompe animals, particularly at frequencies >1 MHz.”

Pompe disease, also known as glycogen storage disease type II (GSDII), is characterized by the accumulation of glycogen in the lysosomes of the cardiac and skeletal muscles. In humans, the onset of Pompe disease may range from the early stages of life to young adulthood, and the disease has a wide spectrum in terms of disease severity.

Despite the fact that the study used mice, this model exhibits the same metabolic and cellular changes as humans; at 6 weeks of age, mice usually develop a considerable amount of intracytoplasmic glycogen content, and by 9 months of age, symptoms become marked with progressive muscle wasting and a weak gait.

Although the authors admit the animal model is a limitation, the results of this publication should be of interest for subsequent studies. “Ex vivo high frequency impedance measures are sensitive to alterations in intracellular myofiber features considered characteristic of GSDII, making them potentially useful measures of disease status,” the authors concluded.

Reference

Nagy JA, Semple C, Riveros D, Sanchez B, Rutkove SB. Altered electrical properties in skeletal muscle of mice with glycogen storage disease type II. Sci Rep. 2022;12(1):5327. doi:10.1038/s41598-022-09328-0