Neurodegeneration in Parkinson’s Disease Lessened by Potential New Drug Class

According to a study recently published in The Journal of Biological Chemistry, researchers from the University of Alabama at Birmingham found a potential new class of drugs to treat Parkinson’s disease after experiments in the brains of rats showed abatement of neurodegeneration and no significant toxicities. The rat model used during the study mimicked two cardinal features of Parkinson’s disease — degeneration of dopamine neurons in the brain, and the accumulation of alpha-synuclein in surviving neurons. Patients with Parkinson’s disease have significant degeneration of dopaminergic neurons in the substantia nigra, up to 70-percent losses at even mid-stages of their disease and abnormal accumulation of α-synuclein in many of the surviving neurons (which occurs years earlier). The potential new class of drugs, kinase inhibitors, are active against the enzyme “leucine-rich repeat kinase 2” (LRRK2, pronounced “lark two”). Two clues point to LRRK2 as a possible target for therapy in Parkinson’s — the first is due to the 2 percent of Parkinson’s disease patients who have a specific mutation in LRRK2 called G2019S which increases the kinase activity of LRRK2, suggesting that increased activity plays a role in progression of the disease. The second is due to rats with no LRRK2 gene who were completely protected from neurodegeneration in the α-synuclein-overexpression model, suggesting pharmacological inhibition may be a viable approach in the future. To read more about his study, click here.