Scientists at the Francis Crick Institute, GlaxoSmithKline and Newcastle University have been investigating the protein LRRK2, which has been identified as potentially playing a role in a number of diseases such as Crohn's, ulcerative colitis, leprosy, tuberculosis (TB) and Parkinson's.
In patients with Parkinson’s disease, an LRRK2 mutation, is often present, and LRRK2 inhibitors have been shown to have the potential to treat the condition, Until recently, however, researchers did not understand the mechanism of disease involved.
The new discovery was achieved through the investigation of LRRK2 in human and mouse macrophages, which are immune cells designed to identify and destroy bacteria. When the macrophages were infected with the bacteria that causes tuberculosis - Mycobacterium tuberculosis (Mtb) – it was observed that the LRRK2 protein prevented the cells from eliminating the bacteria.
If the LRRK2 was removed or blocked in some way, however, the macrophages were able to eliminate the Mtb. Similar results were obtained when the LRRK2 gene in mice was knocked out. The mice were better able to resist TB infection and compared to control mice were found to have less Mtb in their lungs up to two weeks after infection.
These findings may help explain why LRRK2 inhibitors under development for Parkinson’s may be effective. In Parkinson’s, damage in the brain is caused by the formation of abnormal masses of protein called 'Lewy bodies', according to Susanne Herbst, a post-doctoral fellow at the Crick Institute. It is possible that the LRRK2 inhibitors are allowing excretion of the protein and thus prevention of formation of the abnormal masses.
Most research on Parkinson’s to data has focused on degeneration of neurons in the brain. The results of this study, according to Patrick Lewis, an associate professor in cellular and molecular neuroscience at the University of Reading, suggest that a broader approach is needed with respect to investigation of causes of the neurodegeneration that occurs.
It is also possible that the LRRK2 inhibitors being developed for Parkinson’s may also be effective against tuberculosis, according to Max Gutierrez, Group Leader at the Crick. "LRRK2-inhibiting drugs are already being developed to treat Parkinson's disease, and we're trying to see if we can repurpose them as a potential new TB therapy. This should be relatively straightforward because TB infects the lungs, so the LRRK2 inhibitors wouldn't need to cross the blood-brain barrier like they do in Parkinson's disease," he says.
Mr. Walker is the founder and managing director of That’s Nice LLC, a research-driven marketing agency with 20 years dedicated to life sciences. Nigel harnesses the strategic capabilities of Nice Insight, the research arm of That’s Nice, to help companies communicate science-based visions to grow their businesses. Mr. Walker earned a bachelor’s degree in graphic design with honors from London College of Communication, University of the Arts London, England.