Abnormally increased protein kinase activity due to mutations in the leucine-rich repeat kinase 2 (LRRK2) gene is the cause of Parkinson’s (PD) in about 3 to 4% of people with Parkinson's, however researchers have found that most people with Parkinson's do not carry the LRRK2 mutations, which has raised the question of whether LRRK2 therapies might work for others with Parkinson's.

In this study, researchers showed that in brain tissue from individuals with idiopathic PD (of no known cause), LRRK2 kinase activity was higher in vulnerable neurons. The authors proposed that oxidative stress involving alpha-synuclein and mitochondrial impairment activates the LRRK2 kinase activity and that this caused neuron degeneration in the brains of these individuals. Thus, it was concluded that activation of LRRK2 kinase activity, independent of mutations, contributes to the biological mechanisms that lead to  idiopathic PD, suggesting that LRRK2 kinase inhibitors may also be useful for treating both idiopathic Parkinson's and people carrying LRRK2 mutations.

"Our work suggests that the LRRK2-targeted treatments that are being developed for the three percent of Parkinson's patients with LRRK2 mutations may be useful for people without mutations. It's an exciting time for those affected by Parkinson's; disease-modifying therapies are on the horizon," said lead author J. Timothy Greenamyre, MD, PhD, of the Pittsburgh Institute for Neurodegenerative Diseases and the University of Pittsburgh.

The fact that there are a variety of selective LRRK2 kinase inhibitors even for the relatively small number of cases, reflects the interest by the pharmaceutical industry in target-specific therapeutics for PD. 

Read the full paper here: http://stm.sciencemag.org/content/10/451/eaar5429 Roberto Di Maio et al.