Mitochondrial dysfunction v1.0
Research type
Research Study
Full title
Developing non or minimally-invasive measures of mitochondrial dysfunction
IRAS ID
324208
Contact name
Susanne Lewis
Contact email
Sponsor organisation
Newcastle University
Duration of Study in the UK
0 years, 7 months, 18 days
Research summary
Approximately 1 in every 4,000 individuals has Mitochondrial disease. Individuals with mitochondrial disease see on average 8 doctors before they are diagnosed, 75% of patients undergo muscle biopsy and over half are initially misdiagnosed with an alternative condition.
Grip force is a simple and inexpensive clinical test. However, by limiting our measurement to the force of a single grip squeeze, we are missing functionally, and mechanistically relevant information that may help screen and identify patients with mitochondrial disease – especially those with symptoms of exercise intolerance (weakness and/or fatigue during exercise). Therefore, the main aim of this project is to develop a simple, non-invasive measure of mitochondrial function that could be used to screen, identify and monitor patients with mitochondrial disease.
Patients with mitochondrial disease extract less oxygen from the muscles during exercise. We will use a handgrip exercise protocol but, instead of repeated blood samples, we will measure muscle oxygen parameters non-invasively with a technique known as near infra-red spectroscopy. In addition, as there is evidence to suggest that muscle relaxation time might be prolonged with mitochondrial dysfunction, we will use a specially adapted dynamometer (tool to measure muscle force) to measure muscle relaxation time as well as grip force, before, during and after the exercise protocol. Finally, because 7 to 10% of the cellular energy that mitochondria produce is used for electrical signalling we will also use a weak electrical current to directly stimulate muscle and examine its excitability (ability to generate and propagate electrical signals). This technique is known as Muscle Velocity Recovery Cycles.
We aim to recruit 10 patients with genetically confirmed mitochondrial disease and symptoms of exercise intolerance and 10 age and sex-matched healthy volunteers for this pilot study. In addition to the measures described above we will use the Godin-leisure-time-exercise questionnaire to help control for activity levels.
REC name
South West - Central Bristol Research Ethics Committee
REC reference
23/SW/0052
Date of REC Opinion
19 Apr 2023
REC opinion
Favourable Opinion