A pilot study testing a potential treatment for mitochondrial myopathy

Dr Spinazzola and colleagues at University College London (UCL) and Newcastle University are carrying out a pilot study testing a potential treatment in people with mitochondrial disease.


Mitochondria are the parts of the cell that convert most of our food into a usable form of energy. They contain their own DNA, known as mitochondrial DNA, which is inherited from the mother, and is essential for this energy conversion process. If there is a mutation in mitochondrial DNA, the mitochondria will not work properly and many different body systems can be affected. Tissues that use a lot of energy are most severely damaged and, in the case of muscle, this causes weakness, pain and fatigue.

In each cell, there are many copies of mitochondrial DNA and these are usually all identical. However, when a mutation occurs, it may affect some, but not all, the copies. If the proportion of mutated mitochondrial DNA is low then the effects on health may be minimal or non-existent, but once it reaches a certain threshold level then symptoms will appear. Generally speaking, the higher the proportion of mutated mitochondrial DNA, the more severe and extensive the symptoms. Dr Spinazzola and colleagues have recently identified a chemical that promotes the normal but not the mutated mitochondrial DNA in cells in the laboratory. This leads to an increase in the number of healthy mitochondria.

What are the aims of the project?

The main aim of this project is to test this chemical in people with the most common form of mitochondrial disease (caused by a specific mutation, m.3243A>G). The researchers will investigate whether the chemical can find its way to muscle and whether it has the same effect in the body, as it does on cells grown in the laboratory.

This pilot study will take place at the MRC Centre for Neuromuscular Diseases at Queen Square, London, with the participation of clinicians and scientists of the National Hospital for Neurology London and the Newcastle upon Tyne Hospitals NHS Foundation Trust. The chemical will be given by mouth. Throughout the study, the researchers will carefully monitor the participants to determine if the treatment is well tolerated and if the chemical decreases the proportion of mutated mitochondrial DNA.  For these purposes, blood, urine and muscle biopsy samples will be collected at specific time points. The participants will have clearly defined, genetically confirmed disease, and will be recruited through the Medical Research Council Mitochondrial Disease Patient Cohort based in Newcastle and London.

Why is this research important?

This study is essential for establishing the potential benefits of the chemical. Although the treatment showed promising results in cells grown in the laboratory, this is a very different situation to the human body. This small-scale study will provide important information for future clinical trials, such as optimal dosing and safety.

How will the outcomes of this research benefit people with mitochondrial myopathy?

If the chemical is well tolerated and has positive effects on the mitochondria, long-term clinical trials will be investigated to see if the compound could be an effective treatment for people with the m.3243A>G mutation, a condition for which there is currently no cure.

How might this research impact on other neuromuscular conditions?

The chemical could potentially be beneficial for people with other mitochondrial diseases.

Grant information

Project leader: Dr Antonella Spinazzola
Location: University College London
Conditions: Mitochondrial myopathy
Duration: Two years, starting 2018
Total project cost: £146,520

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