Research shows targeting LRRK2 could benefit many with Parkinson's

Studies using human brain tissue and in mice suggest that treatments targeting a protein called LRRK2 have the potential to slow Parkinson's.

You can read the full report published in the journal, Science Translational Medicine.

What is LRRK2?

Parkinson's UK-funded researchers, along with researchers in the US, first uncovered the link between LRRK2 and Parkinson's in 2004.

Changes in the LRRK2 gene, which are the instructions for making LRRK2 protein, are surprisingly common.

Some studies suggest that up to 3% of those with Parkinson's have a mutation somewhere in this gene. However, this still means the vast majority of people do not have a change in the gene.

The LRRK2 protein is involved in many processes in the cell, and mutations in the gene make it overactive which contributes to the loss of brain cells and the development Parkinson's.

What this new research adds

This latest research shows that the LRRK2 protein may be overactive in Parkinson's even when no genetic change is present.

The US-based team designed a molecular 'beacon' that glowed when LRRK2 was active in brain cells.

They discovered that the activity of the LRRK2 protein was elevated in the postmortem brain tissue of people with Parkinson's, and not just those with a change in the LRRK2 gene.

The researchers used a mouse model of Parkinson's to show that overactive LRRK2 prevented brain cells from clearing up the build-up of alpha-synuclein protein.

Using a LRRK2-inhibitor drug molecule, the team were able to block the accumulation of alpha-synuclein, which could play a role in the loss of brain cells in Parkinson's.

Dr Beckie Port, Research Communications Manager, comments:

"Researchers have been interested in the possibility of slowing the progression of Parkinson's by targeting LRRK2 for some time.

"While LRRK2 is one of the most complex genes associated with Parkinson's, a number of potential treatments are moving through the research pipeline. And recently LRRK2 inhibitors have entered phase 1 clinical trials.

"This latest discovery further supports the idea that these treatments could benefit all with the condition, not just those with a change in their LRRK2 gene."