Blood test may help with early diagnosis, before symptoms start

Test would assess Parkinson's-associated damage to mitochondrial DNA

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A new blood test that assesses damage on a particular type of DNA may help in the early diagnosis of Parkinson’s disease, before symptoms start, a new study reports.

“Currently, Parkinson’s disease is diagnosed largely based on clinical symptoms after significant neurological damage has already occurred,” Laurie Sanders, PhD, an associate professor at Duke University School of Medicine, in Durham, and the study’s senior author, said in a university news story.

“A simple blood test would allow us to diagnose the disease earlier and start therapies sooner,” Sanders said, adding that an early “clear-cut diagnosis would accurately identify patients who could participate in drug studies, leading to the development of better treatments and potentially even cures.”

The study, “A blood-based marker of mitochondrial DNA damage in Parkinson’s disease,” was published in the journal Science Translational Medicine.

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Impaired mitochondria linked to nerve cell loss in Parkinson’s

Nerve cell loss in Parkinson’s is associated with the impaired functioning of mitochondria, small compartments inside cells that work as their powerhouses. Notably, mitochondria have their own DNA, the molecule that carries genetic information.

This means that mitochondrial DNA (mtDNA) can suffer damage separately from most of the cell’s DNA, which is stored in a central cellular compartment called the nucleus.

Analysis of brain tissue from deceased Parkinson’s patients as well as preclinical models show evidence of mtDNA damage.

A team of researchers at Duke University previously found brain region-specific mtDNA damage accumulation, along with mtDNA damage increase in tissues outside the brain, in idiopathic (where the cause is unknown) Parkinson’s.

These features were also found in cases linked to mutations in the LRRK2 gene, one of the most common genetic causes of sporadic and familial types of Parkinson’s.

Now, the same team evaluated whether mtDNA damage in blood cells could be used as a biomarker of idiopathic and LRRK2-linked Parkinson’s using a molecular test — dubbed Mito DNADX — that they developed.

To test the efficacy of their test, the researchers analyzed blood cells, called peripheral blood mononuclear cells or PBMCs, previously collected from people with idiopathic Parkinson’s and age-matched healthy people, who served as controls.

Currently, Parkinson’s disease is diagnosed largely based on clinical symptoms after significant neurological damage has already occurred. A simple blood test would allow us to diagnose the disease earlier and start therapies sooner.

Significantly higher levels of mtDNA damage found in Parkinson’s samples

The analysis of the stored samples showed significantly higher levels of mtDNA damage in Parkinson’s samples when compared with controls. The same was seen using PBMCs freshly collected from another group of early idiopathic Parkinson’s patients versus healthy controls.

Significantly higher levels of mtDNA damage were also detected in blood samples from people carrying G2019S, a common Parkinson’s-causing LRRK2 mutation, relative to healthy controls.

This was seen regardless of whether or not they had Parkinson’s symptoms, with no significant differences in mtDNA damage observed between the patient groups.

The analyses were conducted in blood samples collected from patients and age-matched healthy controls who are part of the Michael J. Fox Foundation Fox Bionet group.

The Mito DNADX performed well overall when predicting a Parkinson’s diagnosis, as assessed by the area-under-the curve (AUC). Essentially, AUC values, ranging from 0-1, reveal how well a test performs, with higher values indicating a better ability to correctly identify Parkinson’s cases.

The test’s AUC value was 0.84 for the idiopathic Parkinson’s group, 0.85 for the group of Parkinson’s patients carrying G2019S, and 0.74 for people with the G2019S mutation, but without symptoms.

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No significant differences in mtDNA damage found in people with Alzheimer’s

Notably, no significant differences in mtDNA damage were found between people with Alzheimer’s, another neurodegenerative disease, and healthy people. This suggested that mtDNA damage may be a more specific feature of Parkinson’s.

Given that LRRK2 mutations increase the activity of the LRRK2 enzyme, blocking its activity may have therapeutic potential in Parkinson’s.

With this in mind, the researchers used the test to assess mtDNA damage after exposing lab-grown cells from idiopathic Parkinson’s patients to a LRRK2 suppressor. Results showed that the treatment normalized mtDNA damage levels, as was previously shown in lab-grown cells derived from G2019S-related Parkinson’s patients.

The findings suggest that the Mito DNADX test might help identify patients who benefit from treatment with LRRK2 suppressors, even if they do not carry a mutation on the LRRK2 gene.

“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.”