Isolating a problem’s cause means one can more easily develop treatments to address it. That’s pretty straightforward. So, it’s unsurprising that a new medicine targeting a gene associated with Parkinson’s may make an effective treatment.
What researchers didn’t expect was that this therapy may also help people with the non-hereditary form of the disease.
Shining a Light on the Problem
Mutations in the gene that encodes a protein called LRRK2 only account for 3-4% of Parkinson’s cases. But that still makes this mutation the most common cause of hereditary Parkinson’s disease. The tiny amounts of LRRK2 in affected nerve cells make this protein difficult to study.
Researchers at the University of Pittsburgh School of Medicine and UPMC were studying LRRK2. They engineered a molecular beacon that sticks to the protein to study it better. It glows red under a microscope when it’s active. This showed them where LRRK2 was working in the brain.
Changes in the gene that codes for LRRK2 overactivates the protein. This sets the course of the disease. Researchers thought this LRRK2 activity was only present in the inherited version of Parkinson’s.
Then, the researchers tested LRRK2 levels in brain tissue of people with Parkinson’s disease without the mutation. They also tested brain tissue from healthy individuals. As it turns out, changes in LRRK2 activity may also be responsible for the more common non-hereditary form of Parkinson’s disease.
They checked LRRK2 activity in the dopamine neurons — the brain cells affected by Parkinson’s. In these cells in the brains of people with the disease, LRRK2 was highly active. But not in healthy people.
This suggests that LRRK2 overactivity may be important in all people with Parkinson’s. It’s not just active in those with a gene mutation.
Questioning the Status Quo
Researchers at the University of Pittsburgh School of Medicine and UPMC take on problems differently. J. Timothy Greenamyre, MD, PhD, is a professor of neurology at the University of Pittsburgh School of Medicine. He’s also chief of the Movement Disorders Division at UPMC and director of the Pittsburgh Institute for Neurodegenerative Diseases.
Dr. Greenamyre led the study published in July 2018 in Science Translational Medicine. It details how his team discovered the potential role of LRRK2 in non-hereditary Parkinson’s disease.
“This discovery is extremely consequential for Parkinson’s disease,” said Dr. Greenamyre. “It suggests that therapies currently being developed for a small group of patients may benefit everybody with the disease.”
The Long View
There are approximately 10 million people worldwide with Parkinson’s disease. There is no cure for this progressive disorder of the nervous system — at least not yet. Nobody knows for sure what causes Parkinson’s in about 90% of cases.
With this new understanding and ongoing study, we may someday be able to wipe out the devastation caused by this disease.
Learn more about how UPMC treats people with Parkinson’s disease.
Editor's Note: This article was originally published on , and was last reviewed on .