A lab test that can tell doctors if someone has Parkinson’s disease is a long-sought goal of researchers.
Doctors currently diagnose the progressive condition by looking for telltale physical symptoms: tremors, a halting gait, stiffness or trouble balancing. About 90,000 Americans are diagnosed on the basis of these symptoms each year, according to a recent study.
These signs can be subtle at first, and it can be difficult to discriminate Parkinson’s from other disorders until the disease is more advanced and affects more of the brain.
The lack of a lab test that can pick up the disease in its early stages has also stymied the search for new treatments. Studying a group of people with the same movement symptoms could mean inadvertently including those whose condition could be caused by something else.
It also means people are usually studied when the disease process is well under way. Many therapies work best when they’re given at the first sign of symptoms, or even before.
All this may soon change, thanks to new tests that are able to detect traces of a key protein that misfolds and gums up specific areas of the brain, called alpha-synuclein.
One test, SYNTap, which looks for seeds of this misfolded protein in spinal fluid, was just vetted in the Parkinson’s Progression Marker’s Initiative, a large study undertaken by the Michael J. Fox Foundation. Several companies are developing versions of this type of test.
It joins another test called Syn-One, which detects traces of the protein in skin. Syn-One has been available since 2019 and is being studied with funding from the National Institutes of Health.
When they return positive results, the new tests don’t diagnose Parkinson’s disease but rather point to a group of disorders caused by abnormal clumping of the alpha-synuclein protein. Those include dementia with Lewy bodies and multiple system atrophy, a rare disorder that causes damage to several areas of the brain. Parkinson’s is the most common of these disorders.
Parkinson’s affects the nervous system and, in addition to movement-related symptoms, can cause problems such as depression, anxiety, cognitive impairment, trouble sleeping, hallucinations and loss of smell. It’s not fatal, but it can have serious complications. The exact cause is largely unknown.
The tests usher in “a bit of a new chapter for us in Parkinson’s disease, where we can really focus on biology,” said Dr. Kathleen Poston, a professor of neurology and neurological sciences at Stanford University, who participated in a study of the SYNTap test.
“I think that will very hasten our engagement and clinical trials and, I hope, allow us to have more successful therapeutic clinical trials in in the next five years,” Poston said.
The test is available to doctors, but it had not been shown to be reliable in a large clinical trial.
In a study published Wednesday in the journal Lancet Neurology, the SYNTap test proved to be accurate when given to 1,100 participants, including people with Parkinson’s, people with genetic or clinical risk factors who had not been diagnosed, and healthy controls. Overall, the test correctly identified people with Parkinson’s disease 88% of the time and correctly ruled it out 96% of the time.
“It shows that this method is fairly accurate for detecting Parkinson’s disease, even in patients who do not yet have symptoms,” said Dr. Andrew Ko, a neurosurgeon at the University of Washington School of Medicine who was not involved in the research. “This is a big step forward showing that this type of test is accurate.”
The test was most accurate in people without any known genetic risks for Parkinson’s disease, who also had loss of their sense of smell. In this group, the test correctly detected the disease 99% of the time. If they didn’t have a loss of smell, the accuracy dropped to 78%.
In people with the most common genetic risk, a mutation in their LRRK2 gene, the test correctly flagged Parkinson’s only about 67% of the time.
That means the test is very good at ruling out Parkinson’s, but it will miss some people who actually do have it.
“If you had this test and it was ‘normal’ or negative … it doesn’t mean you don’t have Parkinson’s disease,” said Dr. Kelly Mills, a neurologist and director of the Movement Disorders Division at Johns Hopkins University, who was not involved in the research.
For the time being, that means the test itself won’t be so helpful to individual patients.
“I think it’s a big deal for research, which is going to be a huge deal for patients,” Mills said.
The study’s authors agree.
“Right now, the test has sort of only a modest utility in routine clinical care,” said study author Dr. Andrew Siderowf, a neurologist at the University of Pennsylvania’s Perlman School of Medicine.
Parkinson’s treatment is based on relieving symptoms, and all the test can do is to help a doctor refine a diagnosis. It won’t change how a patient is treated, but it might bring some people peace of mind that their diagnosis is correct, Siderowf said.
It’s also a very invasive test that requires a painful procedure called a spinal tap, although researchers hope to soon translate their results to other kind of biological samples, such as blood or saliva, that would be easier to collect.
One of the most promising results of the study was in people who had early changes that are known to be strongly tied to the development of Parkinson’s disease. In 18 people who had lost their sense of smell, the test detected alpha-synuclein in 16. In another group of 33 people with REM sleep behavior disorder, which makes people kick, punch or hit in their sleep as they act out their dreams, the test detected alpha-synuclein in 28.
Because this group was so small, the researchers say, those tests will have to be repeated to learn whether it can detect the disease before movement is impaired.
But that is the goal, according to the study’s funders at the Michael J. Fox Foundation, who believe that this test will revolutionize research.
“We have a really robust current pipeline of therapeutics that are looking to interfere with the the biology and the disease,” said Deborah Brooks, CEO of the foundation. “We will continue at a rapid and aggressive pace,” she said.
Brooks said that when they learned the results of the SYNTap tests, she flew out to see actor and philanthropist Fox, who was vacationing with his family, to tell him personally. Fox has been living with Parkinson’s since 1991.
Together, they called one of the foundation’s scientists, Dr. Todd Sherer, a neuroscientist who is also the foundation’s chief mission officer.
“I said, ‘so, you know, Todd’s calling in, but he’s gonna tell you all the details. I’m just gonna give you the headline: We’ve had a breakthrough,’ ” Brooks said.
Fox and Sherer had been searching for a biomarker for the condition for over a decade.
When Sherer finished his presentation, Brooks said, Fox leaned over, picked up the laptop and kissed him on the head.
“This is awesome,” he said.