A new test could make it possible to diagnose Parkinson’s disease before symptoms appear, paving the way for early intervention.
According to the results of a nearly decadelong study published April 12 in The Lancet Neurology, a team of scientists with the Parkinson’s Progression Markers Initiative—a longstanding biomarkers study backed by actor Michael J. Fox’s Parkinson’s research nonprofit—described how they developed an assay to detect deposits of a protein called alpha-synuclein in the cerebrospinal fluid of hundreds of at-risk and early-stage patients. The test, recently commercialized by Amprion as SYNTap, was able to distinguish them from non-Parkinson’s patients 88% of the time and had a specificity of 96%.
“It would be difficult to overstate the implications of this discovery,” Deborah Brooks, CEO of the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and a study participant herself, said in a press release. “With development and scaling, αSyn-SAA can usher in the era of objectively and biologically defining Parkinson’s disease—revolutionizing every aspect of research and care.”
SYNTap is a seed amplification assay, or SAA, which were previously used to diagnose neurodegenerative prion diseases like Creutzfeldt-Jakob disease, setting a precedent for their use in diagnosing other brain pathologies involving misfolded proteins. In Parkinson’s, misfolded alpha-synuclein accumulates in the brain as part of what are known as Lewy bodies, which leads to the loss of neurons that signal using the neurotransmitter dopamine. Many of these are in the region of the brain that controls movement, which helps explain why the disease manifests in tremors and other motion problems.
To develop the test, MJFF neuroscience researchers tapped scientists from the University of Texas who were working on an SAA to help diagnose Alzheimer’s. Between 2010 and 2019, they tested it out on cerebrospinal fluid samples from 1,123 individuals, about half of whom had been diagnosed with Parkinson’s. Another 310 had gene changes associated with Parkinson’s but had not yet developed the disease; 51 had early clinical symptoms but didn’t have an official diagnosis, and 163 were healthy controls.
The test was positive for alpha-synuclein deposits at a rate of nearly 99% in patients who had a sporadic form of Parkinson’s—a form without a known genetic cause that makes up about 90% of cases—and who had also lost their sense of smell, one of the condition’s earliest symptoms. It was positive about 78% of the time in individuals who had sporadic Parkinson’s but didn’t have the olfactory deficit and 68% in those who had a form of the disease involving a mutation in the gene LRRK2. LRRK2 is a common target of drugs that are currently in clinical trials for Parkinson's, like Biogen and Denali Therapeutics’ BIIB122 and a small molecule from Qiagen and Neuron23.
To the scientists, these results suggest that not all cases of Parkinson’s may be driven by alpha-synuclein accumulation. LRRK2 mutations are found in a relatively small subset of the Parkinson’s patient population: just 0.5 to 2% of those with the sporadic form and 5% of those with the familial form. Identifying which patients have alpha-synuclein deposits could help researchers find better ways to treat them—potentially before they develop symptoms. The deposits showed up in patients with smell loss and other early hallmarks, such as REM sleep behavior disorder, before dysfunction in the dopamine system was visible on brain scans. That finding validates the notion that alpha-synuclein is part of the disease process that leads to symptoms down the line and that it could potentially be targeted to stave off Parkinson’s altogether, the researchers noted in the press release.
The SYNTap test was granted breakthrough-device designation by the U.S. FDA in February 2022. Physicians can now order the test for people exhibiting Parkinson’s symptoms, though it’s currently not covered by insurance. Amprion offers financial assistance for the test according to patient need, per the company’s website, and is in the process of setting up reimbursement from insurance payers.