Isolating a problem’s cause means one can more easily develop treatments to address it – that’s pretty straightforward. So, it’s not surprising that a pharmaceutical therapy that targets a gene associated with hereditary Parkinson’s disease (currently in development) may translate into a treatment. What researchers didn’t expect was that this therapy may also help people with the non-hereditary form of the disease as well.

Shining a Light on the Problem

Mutations in the gene that encodes a protein called LRRK2 may account for 3 to 4 percent of cases overall, making this mutation the most common cause of hereditary Parkinson’s disease. But LRRK2 is found in extremely small amounts in affected nerve cells, making it difficult to study. A team at the University of Pittsburgh School of Medicine and UPMC engineered a molecular beacon that attached to LRRK2 and glowed red under a microscope only if the protein were active. This showed them where LRRK2 was active in the brain.

The mutation overactivates the protein and sets the course of the disease. But researchers always thought LRRK2 would cause Parkinson’s only in people with the mutation. The researchers tested postmortem brain tissue donated by Parkinson’s patients (none of whom had the mutation) and healthy individuals. As it turns out, non-mutated forms may also be responsible for the more common non-hereditary form.

The test indicated that in the dopamine neurons – the brain cells most commonly affected in Parkinson’s – LRRK2 was highly active in the brains of people with the disease but not in healthy people. This suggests that LRRK2 overactivity may be important in all people with Parkinson’s – not just in those who have a mutation in the gene.

Questioning the Status Quo

Researchers at the University of Pittsburgh School of Medicine and UPMC have a tendency to approach problems from a different angle. J. Timothy Greenamyre, MD, PhD, a professor of neurology at the University of Pittsburgh School of Medicine and chief of the Movement Disorders Division at UPMC (as well as director of the Pittsburgh Institute for Neurodegenerative Diseases), led the study (published in July 2018 in Science Translational Medicine) that 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 because it suggests that therapies currently being developed for a small group of patients may benefit everybody with the disease,” said Dr. Greenamyre.

The Long View

For the approximately 10 million people worldwide with this progressive disorder of the nervous system, there is no cure – at least not yet. Nobody knows for sure what causes Parkinson’s in about 90 percent of cases. But with this new understanding – and with ongoing study – the world may someday see a dramatic decrease in the devastation caused by this disease.