MitoQ & Mitochondrial Dysfunction in MS

Research Summary: MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis

The background

We know that damage to myelin, the substance covering nerves, is a key part of the disability observed in multiple sclerosis.  Whilst many people predict that an autoimmune response is involved, the triggers for that, or other potential causes of damage, remain unknown.

There is increasing evidence that problems with mitochondria and reactive oxygen species (ROS) may contribute to the disease process.  Mitochondria are parts of the cell that are responsible for the majority of the energy production that the body needs.  As part of their normal function, they produce reactive oxygen species.  These ROS are known to have important roles in the body, but under certain conditions (such as inflammation), they can increase to levels that start to cause problems. This is known as oxidative stress and can lead to both cell damage and cell death.

For these reasons, it is thought that targeting mitochondria and ROS may be a new way of treating inflammatory autoimmune conditions, which also avoids many of the side-effects of current medication.

MitoQ is a variation of an antioxidant called Coenzyme Q10. MitoQ has been specifically designed to improve Coenzyme Q10’s ability to enter mitochondria and target the source of problems.  It has already been tested in animal models of Alzheimer’s disease and vascular disorders, where it was shown to be successful in reducing ROS.  The effect of MitoQ in MS has not previously been investigated.

The study

This study was undertaken by researchers at the Oregon Health and Science University in Portland.  The study used an animal model of MS called EAE.  Mice were split into the following four groups:

• Normal control mice
• EAE mice that received no treatment
• EAE mice that received pre-treatment with MitoQ
• EAE mice that received treatment with MitoQ after disease onset

The dose of MitoQ used for the treatment had been determined from previous studies.  At the end of the experiments, the effect of MitoQ was assessed.  This was done by monitoring the clinical disability scores of the mice, as well as measuring levels of inflammation, cell death and oxidative stress in the spinal cord and brain.

The findings

Using the process listed above, the researchers managed to make the following conclusion:

• Both pre-treatment (A) and treatment (B) after disease induction resulted in a decrease in clinical symptoms.  This can be seen in the graph below, where the pink line represents mice with EAE and the yellow line shows mice that had received treatment with MitoQ.  The clinical score measures the level of disability observed in the mice.

To try and explain these results, the researchers then went on to examine a number of other factors in these mice.  From this they saw that:

• MitoQ reduces markers of inflammation in the spinal cord of mice with EAE
• MitoQ suppresses general inflammation in EAE mice
• MitoQ appears to have a neuroprotective effect in two different models of MS
• This neuroprotective effect may result from the fact that MitoQ increases the expression of a gene called STAT-3.  STAT-3 is a gene that is known to be involved in preventing cell death.

The outcomes

To learn more about the outcomes of this research, a detailed Feature Week was conducted with the team at MitoQ Ltd between November 14 – 18, 2016.  The event can now be reviewed in full here.