Developing non-invasive biomarkers of skeletal muscle health in mitochondrial disease using Motor Unit MRI

Principal Investigator: Professor Roger Whittaker

Mitochondrial diseases affect 1 in 4,500 people, with muscle weakness and fatigue being common symptoms. Several clinical trials have suggested exercise as an effective treatment, and have shown how this works in animal models. However, a major barrier to clinical trials is the lack of sensitive biomarkers of this effect in humans. Current techniques such as needle electromyography and muscle biopsy are painful, time consuming, sample only a tiny volume of muscle and are unsuited to repeated measures.

Magnetic Resonance (MR) spectroscopy overcomes many of these limitations, but requires specialist equipment which is not widely available clinically.

We recently developed Motor Unit Imaging (MUMRI); a novel technique capable of non-invasive measurement of human skeletal muscle motor unit structure and function using standard MRI sequences. This includes the ability to measure the twitch dynamics, and hence functional subtype of individual motor units. To assess this as a potential trial biomarker, we will perform a feasibility study involving 15 patients with single mitochondrial deletion and lower limb weakness.

We will assess MUMRI-measured twitch dynamics of the tibialis anterior muscle at baseline, and following 12 weeks resistance training. We hypothesise that MUMRI is at least as sensitive as current non-invasive techniques, to changes in motor unit function and structure, within the time-frame of a feasible clinical trial.

Image: supplied by the research team – shows a colour-coded 3D image of three motor units, imaged in the lower leg of a healthy volunteer, taken using novel MRI scan method (MUMRI). The team will use this technique to study changes in motor unit structure in response to exercise in patients with mitochondrial disease.