Why fixing mitochondria could be the key to Parkinson's

What are mitochondria?

Did you know our brains make up just 2% of our total body weight, yet they use 20% of all our energy reserves? So the brain is particularly reliant on the tiny batteries found in cells known as mitochondria.

Mitochondria are the brain's source of power. They move around our cells, delivering energy wherever it's needed to enable our cells to do their jobs.

Although we talk about mitochondria being the batteries of our cells, there is much more to them than just energy production.

Research has revealed that they play a central role in many other important activities. Let's take a closer look at some of their key functions:

• Converting energy - mitochondria convert the food we eat into energy that the cell can use to perform its function. 
• Cell death and cell protection - when cells become old or damaged they need to be removed. Mitochondria are crucial in managing the process of cell death.
• Managing calcium - calcium is vital for a number of activities in cells, including the release of chemicals called neurotransmitters, such as dopamine, from brain cells. Mitochondria help control the level of calcium inside cells.

So if and when mitochondria become damaged and stop working properly, the effects go beyond a loss of energy. Many other processes and activities inside cells are impacted.

What happens to mitochondria in Parkinson's?

It has been shown that mitochondria stop working properly in Parkinson’s. This is thought to play a role in the death of dopamine-producing brain cells.

• Cells with damaged mitochondria (especially brain cells) may not have enough energy to function properly, triggering a chain of events that ultimately leads to cell death. 
• Dysfunctional mitochondria can produce dangerous levels of harmful factors, called reactive oxygen species, that contribute to cell stress and ultimately cell death. 
• Just like regular batteries, mitochondria wear out and when they do, they need to be recycled and replaced with healthy mitochondria. This recycling process has also been shown to be impacted and less efficient in Parkinson's. 
• We also know that some of the key genes that have been identified as playing a role in Parkinson's are linked to the production or function of mitochondria. For example, changes in the PRKN gene can be a risk factor for Parkinson's. PRKN produces a protein called parkin, which is involved in maintaining the mitochondria.

Finding ways to fix problems with mitochondria

If we can find ways to correct problems with damaged mitochondria, we may be able to develop drugs that can protect brain cells and slow or stop the progression of Parkinson's.

However, while mitochondria are tiny they are still extremely complex and mysterious. We don't know how and why they stop working properly in Parkinson's, and therefore we don't know exactly how to fix them.

That's why we’re investing in exciting projects through the Parkinson's Virtual Biotech programme to support companies that are pioneering new drugs that aim to address problems with mitochondria.

NRG therapeutics

In July 2019, we announced our partnership with NRG Therapeutics Ltd to find ways to boost the functioning of mitochondria in Parkinson's.

NRG has designed small molecules that are able to pass across the blood brain barrier and patch up a hole in the mitochondria wall to help prevent the loss of energy and cell death.

Building on the success of the project, in 2022 NRG secured funding worth £16m, including further investment from the Parkinson's Virtual Biotech. This funding will be used to continue developing these molecules and progress them towards clinical trials.

This offers hope as a potential way to protect mitochondria and help stop brain cells from dying.

Lucy Therapeutics

In June 2024, we announced a partnership with Lucy Therapeutics and the Michael J. Fox Foundation for Parkinson's Research to drive forward research looking at a new drug to restore mitochondria.

Lucy Therapeutics have developed molecules that early experiments show can target a key part of the mitochondria and improve its function. With investment from this partnership, they will look to see in more detail how the molecule might be able to protect brain cells. They’ll be looking at:

• whether the molecule can cross from the blood to the brain
• whether it can reduce build-up and clumps of a protein thought to damage brain cells
• whether it can protect brain cells from damage
• whether it produces any unwanted side effects.

This testing should hopefully improve understanding about how the new drug could work, and would bring it closer towards the next stage of testing in clinical trials.

Mission Therapeutics 

In July 2024, we announced a partnership with Mission Therapeutics and the Michael J. Fox Foundation for Parkinson's Research to see whether a potential new treatment, MTX325, is safe, gets into the brain and improves energy production in brain cells of people with Parkinson's. 

MTX325 has been designed to help get rid of faulty mitochondria. By removing ‘problem mitochondria’ the team hope to protect dopamine-producing brain cells and ultimately slow or even stop the progression of the condition.

MTX325 is currently being tested in healthy individuals to understand its safety. This is vital as it is the first time this compound is being given to people. It then plans to be trialed in 50 people with Parkinson’s, over 28 days, across multiple sites in the UK and other European countries.

The clinical trial is in the planning stages and we hope there will be an opportunity for a small number of people with Parkinson's in the UK to take part. 

The trial is not yet open to recruitment, but you can stay up to date by signing up to receive regular emails with research news and opportunities through our Research Support Network. 

If this small, early stage clinical trial is successful then larger trials would be needed to continue to uncover the potential of MTX325 to protect the brain cells that are lost over time in Parkinson’s.
 

Getting closer to game-changing treatments

Decades of investment have helped us reach the point where exciting ideas for new treatments targeting mitochondria are becoming a reality.

There is still lots of careful work to do in the lab to develop these potential new drugs. And it 's great that some examples are reaching clinical trials to see whether they can deliver on their potential to slow or stop Parkinson's - something no current treatment can do.