Blocking specific neuron interaction may slow Parkinson's progression

BIRMINGHAM, Ala., July 20 (UPI) -- Blocking the action of a mutated kinase enzyme may prevent the formation of proteins key to the progression of Parkinson's disease, according to a newly published study.

Two experimental drugs that block LRRK2 kinase enzyme were shown to lessen aggregations of alpha synuclein protein, which have been shown to play a role in the development of Parkinson's disease, report researchers at the University of Alabama Birmingham.

In addition to Parkinson's disease, alpha synuclein proteins play a role in Lewy body dementia, Alzheimer's disease and other neurodegenerative disorders, though the researchers focused on Parkinson's development.

"These data give us hope for the clinical potential of LRRK2 kinase inhibitors as effective therapies for Parkinson's disease," Dr. Laura Volpicelli-Daley, a researcher at the Center for Neurodegeneration and Experimental Therapeutics at the University of Alabama Birmingham, said in a press release. "The LRRK2 kinase inhibitors may inhibit the spread of pathologic alpha-synuclein, not only in patients with LRRK2 mutations, but in all Parkinson's disease patients. Future studies to validate the safety and efficacy of the LRRK2 inhibitors will be necessary before testing the inhibitors in human clinical trials."

For the study, published in The Journal of Neuroscience, researchers developed a model to cause the formation of alpha-synuclein inclusions in mice similar to those found in Parkinson's disease, which were used to test the effects of LRRK2 on the growth of the proteins.

Two preclinical drugs were then shown to inhibit the expression of the mutant form of LRRK2, which limited growth of alpha-synuclein proteins, when compared to over expression of the normal form of the LRRK2 protein.

"These results demonstrate that alpha-synuclein inclusion formation in neurons can be blocked and that novel therapeutic compounds targeting this process by inhibiting LRRK2 kinase activity may slow progression of Parkinson's disease-associated pathology," researchers wrote in the study.