Exploring new drugs to boost energy in brain cells

As Parkinson’s progresses, certain cells in the brain become more and more damaged and start to die. This is what leads to some of the over 40 symptoms of Parkinson’s. But it’s not clear why this starts to happen.

One of the clues as to why these cells begin to die is that they are not able to produce enough energy to perform their job. Cells that are impacted in Parkinson’s are responsible for producing a brain chemical called dopamine, which helps pass on messages between brain cells. Producing dopamine requires a lot of energy. In all cells, energy is supplied by a part of the brain cell called the mitochondria. This is essentially the ‘battery’ of the cell.

In order to meet the high energy demand of the dopamine producing cells, the mitochondria need a lot of their own genetic information, called mitochondrial DNA. This contains the instructions to make all the different parts of the mitochondria. But, there’s evidence to suggest that levels of mitochondrial DNA are lower in brain cells of people with Parkinson’s compared to people without the condition.

Pretzel Therapeutics have developed a compound that might be able to boost levels of mitochondrial DNA. Through our drug accelerator award programme, we’ve awarded them £200,000 to further test the compound and see if it’s able to boost energy production in cells that are affected in Parkinson’s.

What will the researchers do?

The team at Pretzel Therapeutics will test their designed compound in brain cells in the lab. They want to see if it increases mitochondrial DNA levels, and in turn boosts the amount of energy in the cell. If this is successful, they’ll then move to see if it can do the same for mice that are showing Parkinson's-like symptoms.

What could this mean for Parkinson’s research?

Previous research, including studies using brain tissue by the Parkinson’s UK Brain Bank, have suggested that boosting energy in dopamine producing brain cells could help prevent the cells from dying. By showing that the compound can help keep brain cells producing enough energy, this could be good evidence to potentially run larger studies to see if it can slow the cell death, and in turn the progression of Parkinson’s symptoms.

Professor David Dexter, Director of Research at Parkinson’s UK, said:

“We’re excited to be funding Pretzel Therapeutics to take early but important steps in the development of a compound that has potential for the treatment of Parkinson’s. Targeting the mitochondria, specifically boosting levels of mitochondrial DNA, could lead to us finding a way to slow or stop Parkinson’s, something that no treatment can currently do. “