A new study led by researchers from Michigan State University in Grand Rapids found that people treated with tricyclic antidepressants were less likely to require drug treatment for Parkinson's disease.
On further investigation, the researchers found that rats treated with the tricyclic antidepressant nortriptyline demonstrated a reduction in levels of abnormal alpha-synuclein (a-synuclein) protein in the brain.
Lead study author Tim Collier, of the Department of Translational Science and Molecular Medicine at Michigan State University, and colleagues recently reported their findings in the journal Neurobiology of Disease.
Parkinson's disease is a progressive neurological disorder characterized by tremors, limb stiffness, and problems with movement and coordination.
Around 60,000 people in the United States are diagnosed with Parkinson's every year, and up to 1 million people in the U.S. are living with the disease.
A buildup of the protein a-synuclein is considered a hallmark of Parkinson's disease. Though this protein is present in the healthy brain, in the brains of people with Parkinson's, it can form toxic clusters that destroy nerve cells.
As such, researchers are on the hunt for ways to reduce a-synuclein buildup in the brain, with the aim of slowing Parkinson's disease progression. The new study from Collier and team may have identified such a strategy.
Nortriptyline and Parkinson's
The researchers first uncovered the potential of tricyclic antidepressants as a treatment for Parkinson's disease by gathering patient data and studying the link between antidepressant use and the use of a Parkinson's drug called levodopa.
"Depression is a very frequent condition associated with Parkinson's, so we became interested in whether an antidepressant could modify how the disease progresses," notes Collier.
To test this theory, the researchers treated rat models of Parkinson's disease with the tricyclic antidepressant nortriptyline.They found that patients who used tricyclic antidepressants were less likely to require levodopa therapy, suggesting that tricyclic antidepressants might help to slow the progression of Parkinson's.
Nortriptyline first received approval from the U.S. Food and Drug Administration (FDA) as a treatment for depression in the 1960s.
Nortriptyline prevents a-synuclein clustering
The experiment revealed that nortriptyline led to a reduction in a-synuclein accumulation in the rats' brains.
On further investigation in a cell model, the team found that nortriptyline speeds up the process by which a-synuclein proteins move and change shape, which prevents them from forming toxic clusters.
"The idea that this clustering effect is controlled by how fast or slow a protein reconfigures itself is typically not a standard way of thinking in research on proteins, but our work has been able to show these changes," says study co-author Lisa Lapidus, of the Department of Physics and Astronomy at Michigan State University.
"What we've essentially shown is that an already FDA-approved drug that's been studied over 50 years and is relatively well tolerated could be a much simpler approach to treating the disease itself, not just the symptoms."
The researchers hope to test the safety and efficacy of nortriptyline as a Parkinson's treatment in clinical trials.
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