Positive results from an early clinical trial for a drug boosting cell batteries in people with Parkinson’s

When looking for new treatments for Parkinson’s, researchers also look at existing drugs that are used to treat other conditions. They do this because these drugs will already have lots of data that show the drug is safe for humans to use. 

A drug called UDCA has been used to treat a type of liver disease for over 30 years. But previous research has shown that it might also be able to improve how well mitochondria, the energy producing centre of the cell, work in brain cells.

Mitochondria are in all cells in the body. Previous research has linked problems with mitochondria to Parkinson’s, including in those who have hereditary Parkinson’s. Energy is required by cells to carry out all their processes, including for the production of dopamine, the chemical that is lost in Parkinson’s. If brain cells aren't making enough energy, they can die. Researchers think that by improving the function of the mitochondria, this can protect brain cells. 

What were the aims of the clinical trial? 

The main aim of the phase 2 clinical trial was to confirm whether a high dose of UDCA was safe for people with Parkinson’s. 

The second aim of the trial was to provide evidence that UDCA was having an effect on the cell batteries in the substantia nigra, which is where dopamine cells are lost in the brain in people with Parkinson’s. 

The third aim was to assess whether UDCA had any effect on the movement symptoms of Parkinson’s.

What did the clinical trial involve?

All participants in the trial were people with Parkinson’s who had been diagnosed within 3 years of the trial and who had a stable response to dopamine-replacement medication for more than 3 months. 

The trial took place at Sheffield Teaching Hospitals and University College London Hospitals, and participants attended their site every 12 weeks for safety and symptom measurement tests to take place. 

20 participants received UDCA and 11 received the dummy drug. For those taking the drug, the amount of it they received started small and increased slightly every 3 days, until they were on a high dose of UDCA. The trial took place over 48 weeks (nearly a year). 

What were the results?

There were no serious side effects for those who were taking the UDCA drug. This shows that UDCA can be well tolerated by people with Parkinson’s. The most common side effects were mild gastrointestinal issues such as diarrhoea and nausea, which resolved themselves within 2 to 3 days. This confirms results seen in previous trials for other conditions. 

To measure the changes in the brain cells, the research team used a brain scanner that detects how well mitochondria were producing energy. People who had received the drug had improved mitochondria activity, suggesting that the drug helped to boost energy production. 

Clinical assessment tests of movement showed that there was no change in movement abilities, but in the dummy drug there was a slight improvement, but not by a significant amount. This needs investigating further. They also used another method to measure changes in movement which was a wearable motion sensor that measured changes in gait (the way someone walks). There was an increase in the number of steps per minute in those receiving the drug, suggesting that an increase in energy could be improving the gait. 

Read the full results in Movement Disorders. 

What’s next?

It is promising that the drug appears to be safe and well tolerated by people with Parkinson’s. But only a small number of people were included in this trial, which makes it difficult to interpret the results. We need a larger trial which runs for a longer period to assess whether UCDA can slow Parkinson’s progression. 

A larger and longer study would also validate whether UDCA can cause long term changes in gait that are due to improved energy production or are actually part of the ability of the drug to slow Parkinson’s.

A few of the participants also reported that the number of UDCA tablets they were required to take in combination with their normal medication was too much, especially if they had problems with swallowing. This is something to consider for the future, as the treatment should not be a burden to people taking it. 

David Dexter, Director of Research at Parkinson’s UK said: 
"I am pleased to see that UCDA treatment in people with Parkinson's was safe whilst stimulating an increase in mitochondrial derived energy in the brain.

“The improvement of gait in a subset of Parkinson's individuals taking UDCA is also promising but we will need to have this confirmed in a larger and longer clinical trial where the ability of UDCA to slow Parkinson's progression can also be assessed"