In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Electrical Impedance Myography Correlates with Functional Measures of Disease Progression in D2-mdx Mice and Boys with Duchenne Muscular Dystrophy
Today’s pick is from Journal of Neuromuscular Diseases by Chrzanowski et al on electrical impedance myography for Duchenne patients and mice. DOI: 10.3233/JND-210787.
Outcome measures are important in Duchenne for measuring therapeutic effects in clinical trials. However, functional outcome measures have a motivation component, which is prone to variation. Objective measures are therefore studied as additional outcomes.
When studying muscle quality, one objective measure is MRI, but this is expensive and can only be done if an MRI is available. Authors offer electrical impedance myography (EIM) as an alternative that is less expensive and can also measure over time (unlike e.g. a muscle biopsy).
EIM studies the resistance, reactance and phase of a muscle after sending an electric current. The resistance will increase when muscle is replaced by fat and fibrosis while the reactance will vary with muscle atrophy or hypertrophy. The phase is a ratio of the two.
Here authors used existing datasets for EIM for d2/mdx and wildtypes of the same background and Duchenne patients and controls to correlate EIM findings with function and histology (mouse only).
As expected Duchenne patients performed worse functionally than controls and d2/mdx had smaller fibers, lower mass and more fibrosis than the wild type and were less strong.
When looking at EIM results for mouse and human (see picture) it is clear there are differences especially for the reactance. However, there is no increase or decrease over time generally. Also there is a lot of variability within groups.
Authors show that EIM values correlate for humans with functional tests (e.g. 10 meter walk) and for mice with muscle strength. Based on this they conclude it could be a good biomarker for disease progression and to use in clinical trials.
I think it is way too early to conclude this. If you want to detect a therapeutic response, you need to be very sensitive. The question is whether a therapeutic response can be picked up with this method given the variation between individuals (mouse and humans).
Authors outline the limitations of the study, which includes that it is difficult to do long term correlations between EIM and function as over time patients will lose a specific function (e.g. 10 meter walk/run cannot be done if patients cannot walk).
They also only studied one muscle so far (gastrocnemius) in mice and humans. More muscles have to be analyzed in the future. I agree – especially the arm muscles as well, given that outcome measures and reference data for non ambulant patients are sorely needed.
Another study that needs to be done is in mice where a known treatment is used to see if EIM can indeed pick up a therapeutic effect. There are many approaches that work preclinically in mice so this would not be too hard and would provide important information on sensitivity.