Stanford Medicine has led a study in mice that suggests inhibiting the LRRK2 enzyme could prevent neuron death in patients with a form of Parkinson’s disease caused by a genetic mutation. The research, published in Science Signaling, indicates that overactivity of the leucine-rich repeat kinase 2 (LRRK2) enzyme disrupts communication between dopamine-producing neurons and cells in the striatum, affecting movement and decision-making.
Suzanne Pfeffer, PhD, professor of biochemistry at Stanford University, stated: “Findings from this study suggest that inhibiting the LRRK2 enzyme could stabilize the progression of symptoms if patients can be identified early enough.” The researchers used MLi-2 LRRK2 kinase inhibitor to decrease enzyme activity.
The study found that overactive LRRK2 causes cells to lose primary cilia, essential for sending and receiving chemical messages. This loss disrupts crucial signaling involving sonic hedgehog proteins necessary for neuroprotection. Pfeffer explained: “Many kinds of processes necessary for cells to survive are regulated through cilia sending and receiving signals.”
The research team tested whether MLi-2 could reverse these effects. After three months of treatment in mice with the genetic mutation, results showed restoration of primary cilia and improved communication between neurons. Pfeffer noted: “These findings suggest that it might be possible to improve, not just stabilize, the condition of patients with Parkinson’s disease.”
The next phase involves testing whether other forms of Parkinson’s disease could benefit from this treatment approach. “We are so excited about these findings,” said Pfeffer. “There are multiple LRRK2 inhibitor clinical trials underway.”
Funding for the study came from The Michael J. Fox Foundation for Parkinson’s Research, Aligning Science Across Parkinson’s initiative, and the UK Medical Research Council.
This story was originally published by Stanford Medicine.
