New blood test detects early Parkinson's disease

A new test detects mitochondrial DNA (mtDNA) damage in blood cells collected from patients with Parkinson's disease.

Parkinson's disease is a neurodegenerative movement disorder that currently has no cure. Most cases occur sporadically (called idiopathic Parkinson's disease), while around 15 percent are caused by genetic factors. Researchers from Duke University in Durham, North Carolina have developed a novel assay that successfully quantified mtDNA damage, which they suggest could be used to help with earlier diagnosis and therapeutic intervention.

'Currently, Parkinson's disease is diagnosed largely based on clinical symptoms after significant neurological damage has already occurred' said Dr Laurie Sanders, from the Department of Neurology and Pathology at Duke University School of Medicine and senior author on the study. 'A simple blood test would allow us to diagnose the disease earlier and start therapies sooner.'

'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'.

Mitochondria have their own DNA, separate from the chromosomal DNA in the nucleus. Both idiopathic Parkinson's disease, and Parkinson's disease associated with the leucine-rich repeat kinase 2 (LRRK2) genetic mutation, have been associated with mtDNA damage.

Published in Science and Translational Medicine, the team used PCR technology to develop the novel assay, called Mito DNADX. The assay successfully identified higher levels of mtDNA damage in peripheral blood cells of patients with idiopathic Parkinson's disease, as well as patients with LRRK2-associated Parkinson's disease compared with age-matched controls. This also included LRRK2 mutation carriers who did not have a clinical diagnosis of Parkinson's disease.

The researchers then investigated whether their assay could determine the effectiveness of a therapy that targets the LRRK2 mutation. The Mito DNADX assay showed reduced mtDNA damage after treatment with an LRRK2 kinase inhibitor called MLi-2, in patient-derived cells and a rodent model of Parkinson's disease, compared to a control treatment. This finding was demonstrated in cells derived from both idiopathic Parkinson's disease and LRRK2-associated Parkinson's disease patients.

Dr Mark Cookson, a neurodegeneration scientist at the National Institute on Ageing in Maryland, told Science: '[the assay] adds to our ability to state confidently that an individual has Parkinson's disease or not'.

In the future, research will include further testing of the assay in patients at the earliest stage of the disease, before symptoms develop and significant neurological damage has occurred.

'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', said Dr Sanders. '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.'