Parkinson's disease is a brain disease that can gradually lead to difficulty in movement, tremors, and eventually dementia.Early diagnosis is often very difficult during its course of several years.DNA damage found in blood samples provides an easy way to diagnose the disease early, a study using rodent and Parkinson's disease tissue has shown.The research was published recently in the journal Science-Transformed Medicine.
While this potential test needs to be validated in clinical studies, blood tests based on these findings could help patients receive existing treatments earlier and facilitate clinical trials to evaluate new treatments, says Mark Cookson, a neurodegenerative disease researcher at the National Institute of Aging.
"It's exciting because doctors can use it to detect Parkinson's disease before clinical symptoms appear.Malú Tansey, a neuroscientist at the University of Florida who was not involved in the study, said.
Parkinson's disease occurs when death of certain neurons in the brain causes a decrease in dopamine levels, a neurotransmitter.Over time, the disease can lead to muscle stiffness, balance problems, speech and cognitive problems, and other symptoms.The disease is linked to environmental and genetic factors that afflict millions of people in the United States.
The new test is based on observations that Parkinson's disease is often associated with mitochondrial failure.Mitochondria are powerful organelles within cells that have their own DNA.Several teams, including a team led by Laurie Sanders, a neurologist at Duke University School of Medicine, reported signs of mitochondrial DNA (mtDNA) damage in brain tissue in some Parkinson's patients.Some studies have also found defects in mitochondria in patients' blood cells, suggesting that blood mtDNA damage "may be a substitute for what happens in the brain.”
Sanders' laboratory and collaborators recently developed a new test to assess the amount of damaged mtDNA in blood samples.The test distinguished groups of up to 50 Parkinson's patients from healthy controls.Researchers found that a patient diagnosed with Parkinson's disease had a higher level of blood mtDNA damage and was born with a rare mutation called LRRK2, which increases the risk of Parkinson's disease.Sanders' team previously linked the mutation to mtDNA damage in brain tissue.
Most interesting of all, the test found the damage in people with no symptoms of LRRK2.Sanders says it shows that it can mark people before they develop a serious disease or even mark them in more than 90 percent of people who lack LRRK2 mutations or other Parkinson's-related mutations.
The trial could also help determine who might benefit from an experimental Parkinson's compound targeting LRRK2.Sanders' team reported that treatment with the compound reduced mtDNA damage in cultured cells and neurons in neurotoxin-induced Parkinson's disease rats.The compound is currently undergoing clinical testing, Sanders said, and the team's analysis could show if it is helpful to patients.
So far, the test has only retrospectively tested stored blood samples; researchers need to pass a prospective test to prove that it can accurately and sensitively detect Parkinson's disease early.Researchers also need to better understand why blocking LRRK2 appears to reduce mitochondrial DNA damage, Cookson said."It is important to understand the mechanisms so that we can understand exactly what this promising biomarker tells us about the pathogenesis of the disease.' he said.
The mtDNA test is not the only blood test candidate for Parkinson's disease.Earlier this year, researchers reported that analysing the misfolded form of a neuroprotein called α-synaptic nucleoprotein in spinal fluid could diagnose 88 percent of 545 existing patients.Researchers are studying blood tests for the protein, which accumulates in the brains of Parkinson's patients.
But the mtDNA and α-synaptic nucleoprotein tests "measured something slightly different," possibly reflecting different forms of Parkinson's disease, Sanders said.She envisioned two tests for people suspected of Parkinson's disease."It gives us a real understanding of what's going on with the disease, so we can treat it better."