Researchers announced results from the largest study yet of a new test to detect Parkinson’s — it confirmed that the test was accurate, even for early Parkinson’s.
There is currently no single test that can confirm a Parkinson’s disease (PD) diagnosis. Doctors rely on symptoms and in-office tests to make a diagnosis, meaning the disease has most likely progressed years before symptoms are present. However, a recent study adds promising new data to bolster support for a test that may allow Parkinson’s to be diagnosed before symptoms appear and may help inform Parkinson’s clinical trials.
A hallmark of Parkinson’s is a protein called alpha-synuclein, which is involved in normal brain cell function. However, for many with Parkinson’s, the alpha-synuclein protein clumps or misfolds, meaning it is not shaped properly. Certain forms of misfolded alpha-synuclein may act as “seeds” that spread and lead to misfolding of healthy alpha-synuclein. These misfolded proteins can clump together, and eventually kill brain cells.
Prior work supported by the Parkinson’s Foundation, has shown that the alpha-synuclein “seeds” can spread from cell to cell, much like the dye from a red sock in the washing machine can turn everything pink. Because these protein “seeds” are at very low levels, researchers have re-purposed technology originally developed 20 years ago to test for prion diseases to amplify the misfolded alpha-synuclein in Parkinson’s. The test is called an alpha-synuclein seed amplification assay (SAA). Several small studies have previously shown that this test can distinguish between people who do or do not have Parkinson’s.
On April 12, 2023 The Lancet published the largest test of alpha-synuclein SAA to-date. Andrew Siderowf, MD, neurologist at University of Pennsylvania, Luis Concha-Marambio, PhD, research and development director at Amprion, and colleagues analyzed samples from 1,123 participants who were enrolled in the Michael J Fox Foundation’s Parkinson’s Progression Markers Initiative (PPMI), which includes individuals from 33 outpatient neurology practices worldwide.
The participants included 163 healthy volunteers, 545 people with Parkinson disease, 54 people who had evidence of the disease on brain scans, 51 people who had conditions that often later develop Parkinson’s (but did not yet have Parkinson’s symptoms), and 310 people who had gene mutations that are associated with Parkinson’s but did not yet show symptoms.
The alpha-synuclein SAA test detected early Parkinson’s 87% of the time. In volunteers who did not have Parkinson’s, the test showed the absence of the disease 96% of the time. Surprisingly, only 70% of individuals with mutations in their LRRK2 gene, which has been associated with Parkinson’s, had abnormal alpha-synuclein. This observation could have implications for LRRK2 treatments that are currently being developed — perhaps not all individuals with LRRK2 mutations will respond equally to the treatment.
The test’s ability to detect early abnormal alpha-synuclein Parkinson’s makes it a promising potential tool. Though it is not currently commercially available for diagnosing Parkinson’s, it may soon become useful in Parkinson’s clinical trials by helping researchers learn more about the individuals enrolled and in recruiting people at earlier stages. An editorial in The Lancet called it “a game-changer in Parkinson’s disease diagnostics, research, and treatment trials.”
Study Results
- Alpha-synuclein seed amplification assay detected early Parkinson’s 87% of the time
- In volunteers who did not have Parkinson’s, the test showed the absence of the disease 96% of the time
What does this mean?
This method of detecting abnormal alpha-synuclein could be an effective way to detect Parkinson’s years before symptoms appear. Earlier detection would allow for earlier treatment once researchers identify a successful disease-modifying drug. In addition, in its current form, the test can only tell if a person has abnormal alpha-synuclein, NOT how much and how it is changing over time.
Additionally, researchers could use this method to recruit people with early-stage Parkinson’s to clinical trials. It could also help determine the effectiveness of treatments in clinical studies. For example, if a drug treatment reduces abnormal alpha-synuclein over time, it could indicate that the treatment is having an effect.
However, a downside to this test is that it requires a lumbar puncture, also called a spinal tap, to obtain samples of cerebrospinal fluid (CSF). A lumbar puncture can be uncomfortable and requires a specialist physician. It may also cause short-term side effects like headache.
Research Springboard
Studying seed amplification assays to detect and monitor the progression of Parkinson’s is a large and growing field of research that brings hope. In 2014, SAA’s were applied specifically to detect alpha-synuclein, and researchers have been working on improving them ever since.
Researchers in the PD field are working to develop a quantitative test — an alpha-synuclein SAA test — that finds the presence of alpha-synuclein and measures the amount of abnormal alpha-synuclein. A test like this could be used to see if the alpha-synuclein amount changes with the disease progression, symptom appearance and specific treatments. The hope is to develop an alpha-synuclein SAA test using samples from blood, nasal mucosa, skin and other body fluids that do not require an invasive procedure.
Concurrently to this study, Parkinson’s Foundation research grantee, Giovanni Bellomo, PhD, is looking into ways to improve the alpha-synuclein SAA test. Dr. Bellomo is studying whether mucus in the nose can be used to detect SAA, instead of cerebrospinal fluid. Early PD-related alpha-synuclein changes can be found in the olfactory mucosa, which is collected using a swab to scrape the inside of the nose. Dr. Bellomo will compare the results of SAAs and olfactory mucosa collected from people with and without PD. This non-intrusive test would represent a breakthrough in Parkinson’s diagnosis, as no such test currently exists.
In addition, he is looking into developing a more clinically useful test that can be reproduced (obtain the same results) in different labs. Lastly, Dr. Bellomo and his team are also developing a way to utilize SAA’s to measure the amount of abnormal alpha-synuclein and how it correlates with movement and non-movement symptoms. The first results of Dr. Bellomo studies were published on April 1, 2023. Learn more about this current study.
What do these findings mean to the people with PD right now?
Although alpha-synuclein seed amplification assay may be available through a doctor’s office, it is not yet a standard of care and it does not change how doctors diagnose and treat PD. Questions remain about interpreting the results, especially for people who have may genetic forms of PD or do not yet show symptoms of PD. Therefore, it will require additional research and time before the test could become useful as part of routine care. In addition, the test is not covered by medical insurance and is cost prohibitive. Nevertheless, studies like this one are an important step toward allowing the medical research field to establish a test that can help doctors diagnose and track disease progression.
Learn More
The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.
