Motor Unit MRI in Mitochondrial Disease
Research type
Research Study
Full title
Skeletal muscle health in mitochondrial disease studied with motor unit MRI
IRAS ID
304444
Contact name
Roger Whittaker
Contact email
Sponsor organisation
NJRO
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Mitochondrial diseases are a group of genetic disorders caused by a genetic defect in the mitochondrial DNA. This leads to an impaired energy production in the cells and therefore especially affects organs with a high energy demand, like skeletal muscle. A prominent feature of mitochondrial disease is therefore a decline in the ability of the muscle to generate force, defined as muscle fatigue.
No curative treatment for mitochondrial disease exists, but studies suggest that exercise has a beneficial effect. Exercise can increase the number of mitochondria, thereby increasing the muscle energy production and muscle strength.
However, sensitive outcome measures to assess this effect in vivo in humans are lacking. Current techniques, like needle electromyography and muscle biopsy, are painful, time consuming, sample a tiny volume of muscle and are unsuited to repeated measures. MR spectroscopy overcomes many of these limitations but requires specialist equipment. We recently developed Motor Unit Magnetic Resonance Imaging (MUMRI), a 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 fatigability of individual motor units.
To assess MUMRI as a potential trial biomarker we will perform a feasibility study. Fifteen patients with mitochondrial disease (single deletion) will receive 12 weeks of resistance exercise training of the lower limbs. At the start and end of this exercise programme, an MUMRI scan of the lower leg will be acquired to assess the motor unit twitch dynamics and fatigability. The MRI outcome measures will be compared to current outcome measures like structural imaging, measures of disease burden and muscle strength/function.
This pilot trial will act as a proof of principle trial in patients with single-deletion mitochondrial disease and will provide vital data to underpin MUMRI as a non-invasive outcome measure for future clinical interventional trials.
REC name
North West - Liverpool Central Research Ethics Committee
REC reference
21/NW/0316
Date of REC Opinion
16 Nov 2021
REC opinion
Favourable Opinion