A blood test that can identify Parkinson’s disease may help in the early diagnosis of the disorder and prevent further harm to the nervous system.
Parkinson’s disease, which affects 10 million people globally and is the second-most prevalent neurological disease after Alzheimer’s, would greatly benefit from the development of a novel blood-based diagnostic test. The study was led by a group of neuroscientists from Duke Health and published on August 30 in the journal Science Translational Medicine.
“Currently, Parkinson’s disease is diagnosed largely based on clinical symptoms after significant neurological damage has already occurred,” said senior author Laurie Sanders, Ph.D., an associate professor in Duke School of Medicine’s departments of Neurology and Pathology and member of the Duke Center for Neurodegeneration and Neurotherapeutics.
“A simple blood test would allow us to diagnose the disease earlier and start therapies sooner,” Sanders said. “Additionally, a clear-cut diagnosis would accurately identify patients who could participate in drug studies, leading to the development of better treatments and potentially even cures.”
Sanders and coworkers focused on mitochondrial DNA damage as a biomarker for their diagnostic tool. Cells’ mitochondria are factories that transform unprocessed energy into a form that powers them. They have their own DNA, which is susceptible to damage, apart from nuclear DNA, which contains the majority of an organism’s genome.
The Duke-led research had previously found an accumulation of mitochondrial DNA damage, especially in the brain tissue of deceased Parkinson’s patients. Previous studies have linked mitochondrial DNA damage with an increased risk of Parkinson’s disease.
Using polymerase chain reaction (PCR) technology, the Duke team developed an assay that successfully quantified higher levels of mitochondrial DNA damage in blood cells collected from patients with Parkinson’s disease compared to people without the disease.
The new test also identified high levels of damaged DNA in the blood samples of people who harbor the genetic mutation LRRK2, which has been associated with an increased risk of the disease. The assay was able to detect patients with Parkinson’s disease with and without LRRK2 mutations.
The new test also found that blood samples from people who have a mutation in the gene LRRK2, previously linked to an elevated risk of the disease, contained substantial levels of DNA damage. Parkinson’s disease patients with and without LRRK2 mutations might be found using the assay.
The effectiveness of a medication that targets the consequences associated with the LRRK2 mutation was investigated in detail in cells from Parkinson’s disease patients using the team’s PCR-based test.
In comparison to samples from individuals who did not receive the LRRK2 inhibitor, the test on these samples revealed decreased levels of mitochondrial DNA damage in cells treated with the inhibitor. This shows that even if a patient does not have an LRRK2 mutation, the assay may still be able to identify Parkinson’s disease patients who would benefit from LRRK2 kinase inhibitor therapies.
“Our hope is that this assay could not only diagnose Parkinson’s disease, but also identify drugs that reverse or halt mitochondrial DNA damage and the disease process,” Sanders said. “This disease takes a terrible toll on people, and we are still just treating the symptoms. It’s important to get new, effective treatments over the finish line.”
Further evaluation of the assay with samples from patients in the very early stages of the disease, before symptoms appear, will be done by the study team in the future, according to Sanders.
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