(CN) — Proteins in the blood may provide key indicators of the inflammatory process that takes place in the early stages of Parkinson’s disease which is likely to allow for broader clinical trials focused on preventing the disease's debilitating symptoms, according to a new study published in Nature Communications.
The study authors say that a blood test for a specific panel of proteins can be used to predict the development of Parkinson’s disease seven years before the onset of physical symptoms.
Parkinson’s disease is a degenerative condition that affects the nervous system causing motility problems such as tremors, rigidity, slowness and lack of balance. The disease also affects non-motor systems causing dementia, psychosis, mood and behavior changes and sleep disorders.
Globally, 10 million people are affected by the disease, and it is one of the fastest growing neurological disorders. However, there are still gaps in scientific knowledge regarding the molecular processes that occur at the earliest stages of the disease. Researchers involved in the study believe that upcoming clinical trials will shed light on how to interrupt a cascade of effects that lead to nervous system degeneration.
“The test enables us to diagnose and predict if the subjects will develop Parkinson's disease or not with a very small amount of blood, ten microliters, just a spot,” said Dr. Michael Bartl, clinical scientist in the Neurology Department at the University Medical Center, Göttingen, Germany.
According to Bartl, one of the barriers to developing effective therapies for the disease is that the current testing methodologies only allow clinical researchers to evaluate new drugs in trials with patients who are already in the advanced stages of neurodegeneration.
“Usually at this stage most of the neurons for cells in the brain are already gone, and there is a theory that a lot of the trials fail because they come too late,” Bartl said. With earlier diagnoses, researchers will be able to test prevention strategies before nerve cells are widely damaged, allowing for better measurement of test outcomes and, potentially, prevention of further degeneration.
Current testing for Parkinson’s disease involves an invasive puncture in the lumbar spine to collect cerebrospinal fluid, often referred to as a spinal tap. A blood test for the disease may open the door to larger scale research trials, because it will be easier and more efficient for patients to participate due to the less invasive test, Bartl said.
In order to find these indicators of the early stages of Parkinson’s, researchers tested the blood samples of four different test groups for proteins that prior research suggests are connected to inflammatory processes related to the disease. Two control groups were made up of healthy individuals and individuals with other neurological disorders, a third group was made up of those diagnosed with Parkinsons and final group was made up of individual with a sleep disorder who often develop Parkinson’s later in life.
REM Sleep Behavior Disorder (RBD) is a condition in which the body moves in conjunction with dreams that are vivid or involve physical action. Patients who have this disorder can unconsciously strike themselves or a bed partner when physically acting out dreams.
Normally, when the body goes into REM sleep and begins to dream, the nervous system initiates a paralysis that prevents the body’s physical response to dreams. The disorder is a malfunction of this process and an early sign of nervous system deterioration — around 80% of patients with the condition go on to develop Parkinson’s.
The researchers found the abnormal levels of eight proteins in both the Parkinson’s test group and the REM Sleep Behavior Disorder test group but not in the control groups of healthy test subjects or subjects with other neurological disorders.
The researchers then used a machine learning model to analyze blood samples from all the test groups based on the composition of the eight proteins. The model was able to identify full onset Parkinson’s disease in the test blood samples with 100% accuracy.
Testing data included samples taken from patients over a 10-year period and within that time some of the test subjects with REM Sleep Behavior Disorder progressed to develop Parkinson’s disease.
The machine learning model was able to predict which of the RBD subjects would later develop Parkinson’s with a 79% accuracy from blood samples taken up to seven years prior to the onset of motor symptoms.
Along with early diagnoses, the proteins identified in the research may also provide insight into the inflammatory processes at the very beginning stages of neurodegeneration.
“The test is based on proteins that are involved in the pathophysiology of the disease,” Bartl said. “So, these are all potential targets for therapies because we know there is an imbalance creating more inflammation and less protection."
One of the proteins identified in the study is also associated with cellular health in cancer research and medications are already available that interact with that protein. Bartl said that existing medications and other prevention strategies are likely to be part of future research trials, and blood testing may allow test subjects from around the world to participate in trials by mail.
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