A new test may be able to predict Parkinson's disease years before symptoms occur by detecting biomarkers in spinal fluid. And while the test cannot replace an expert diagnosis, many experts believe it could "shape how and when we diagnose Parkinson's." 

Top drivers of change in the neurodegenerative disease market

What you need to know about Parkinson's disease

Every year, around 90,000 Americans are diagnosed with Parkinson's disease, making it the fastest-growing neurodegenerative condition in the United States. The disease is caused by the buildup of abnormal proteins called alpha-synuclein in the nervous system and brain.

Currently, there is no blood or laboratory test that diagnoses the condition, according to Michael Henderson, a neuroscientist at the Van Andel Institute.

Previously, diagnoses relied heavily on the presentation of symptoms, including slowness, stiffness, tremors, and balance issues. However, those symptoms often overlap with other brain disorders, leading to 10% to 20% of patients being misdiagnosed with Parkinson's.

Experts believe the buildup of alpha-synuclein begins years before patients notice physical symptoms. Typically, by the time a patient starts experiencing symptoms, they are estimated to have already lost as many as 80% of their dopamine-making cells.

A 'breakthrough' in Parkinson's testing

Now, a new test that uses spinal fluid to detect biomarkers may be able to predict Parkinson's disease years before symptoms occur. According to scientists at the  Parkinson's Progression Markers Initiative (PMMI), the test, called the alpha-synuclein seed amplification assay (αSyn-SAA), screens patients' spinal fluid for synuclein pathology, which is one of the two biological markers of Parkinson's disease.

In a study sponsored by the  Michael J. Fox Foundation, researchers evaluated the αSyn-SAA test. Between July 2010 and July 2019, study participants were recruited from 33 academic neurology outpatient practices around the world.

Overall, the researchers evaluated 1,123 participants, including 545 who were diagnosed with Parkinson's, 51 people diagnosed with prodromal Parkinson's, 310 asymptomatic carriers of Parkinson's-associated genes, 54 people with parkinsonism who had scans with no evidence of dopamine deficiency, and 163 controls.

According to the researchers, the test could detect Parkinson's in 87.7% of cases and was able to screen out participants without the disease in 96.3% of cases. It could also detect the disease in 98.6% of participants who experienced prolonged loss of smell.

"While loss of smell appears to be a strong predictor of Parkinson's disease, it's important to note that this study identified individuals with positive alpha-synuclein SAA results but who had not yet lost their sense of smell, indicating that alpha-synuclein pathology may be present even before there is a measurable loss of sense of smell," said co-author Tanya Simuni of  Northwestern University.

While the test cannot replace an expert diagnosis, it could "shape how and when we diagnose Parkinson's," said Rachel Dolhun, SVP of medical communications for the Michael J. Fox Foundation.

The αSyn-SAA test is already "unlocking new understanding of Parkinson's," said Kenneth Markek, principal study investigator of the PMMI and president and senior scientist at the  Institute for Neurodegenerative Disorders. 

Markek also noted that he expects the findings "will transform every aspect of drug development and ultimately clinical care. We will rapidly be in a position to test new therapies in the right populations, target the right therapy to the right patient at the right time, and launch studies of agents with potential to prevent Parkinson's disease altogether."

"Identifying an effective biomarker for Parkinson's disease pathology could have profound implications for the way we treat the condition, potentially making it possible to diagnose people earlier, identify the best treatments for different subsets of patients, and speed up clinical trials," said study author Andrew Siderowf of the  University of Pennsylvania.

"In no uncertain terms, this is a major breakthrough with unprecedented implications for the future of Parkinson's, drug development and ultimately clinical care," said Deborah Brooks, CEO of the Michael J. Fox Foundation. (George, MedPage Today, 4/12; Dean, Becker's Clinical Leadership & Infection Control, 4/13; Herper, STAT, 4/12; Jarvis, Bloomberg/Washington Post, 4/13; Rodriguez, USA Today, 4/14; Siderowf et al., Lancet Neurology, 5/2023)

Why this 'breakthrough' test may not be adopted as soon as you think

By Julia Elder and Lindsey Paul

The ability to detect Parkinson's disease through a biomarker test is a significant milestone. However, as we've learned from  multi-cancer early detection tests, adoption of this diagnostic test may not be as imminent as it seems.

1.    Clinical utility is necessary for adoption

Through our research into the  early cancer detection landscape, we have learned that many providers and payers are unwilling to adopt diagnostic tests without some assurance that the testing will impact patient outcomes. Because diagnostic testing can be costly, invasive, and stressful for patients, proof of utility is a key component of patient-centered care.

In addition to preventing unnecessary testing, proof of utility safeguards clinicians from increased workloads. As we've seen with liquid biopsies for cancer detection, new diagnostic tests are often used in combination with existing diagnostic tools. Still, some clinicians may be hesitant to implement a new diagnostic tool unless they see evidence of a clinical benefit.

In discussions about early cancer detection, payers have told us they often rely on proof of utility when making coverage decisions. Denying coverage for unproven tests reduces spending on potentially low-value tests. Why pay for patients to receive an expensive test that won't change their disease outcomes?

These concerns are also relevant when considering the new diagnostic test for Parkinson's. Currently, there are no treatments that can slow or reverse disease progression. In addition, the αSyn-SAA test involves an invasive procedure to retrieve a cerebrospinal fluid sample, which is a burden to patients and providers. Ultimately, early diagnosis of Parkinson's could lead to unnecessary stress for patients and costs to the healthcare system with little benefit.

Until more therapies are developed to treat Parkinson's, it will be difficult for any diagnostic to demonstrate utility or gain adoption.

2.    Diagnostic discoveries can drive innovation

While this discovery may not have an immediate impact, it mirrors the ongoing research trend of identifying biomarkers for neurodegenerative diseases. Despite the lack of evidence of utility, the development of a biomarker-based diagnostic for Parkinson's disease can still support future research.

For example, the early cancer detection industry has shown us that new biomarker identification can  drive treatment innovation. In particular, life sciences companies might be more willing to invest in developing treatments for Parkinson's disease now that a biomarker has been identified.

The αSyn-SAA test can differentiate between subtypes of Parkinson's disease, which could lead to precision medicine for Parkinson's disease treatment — similar to the discovery of the BRCA gene in breast cancer subtypes.

Overall, this discovery is a huge step in understanding Parkinson's disease — even if it may not lead to immediate changes in clinical practice. 

Four key drivers shaping the care outlook for patients with neurodegenerative diseases

As occurrence of neurodegenerative disease in the U.S. has increased, advances in medicine have expanded the outlook for diagnosing, treating, and curing these diseases. We’ve identified four key drivers that are changing the treatment prospect and delivery of care for patients with neurodegenerative diseases. Download the report here