Currently, Parkinson’s disease (PD) diagnosis is based on a visual clinical exam, done by a doctor (ideally a neurologist or movement disorder specialist) in their office. This means that motor symptoms such as tremor, stiffness and slowness must be apparent before a diagnosis is made by the neurologist – yet those visible symptoms don’t often appear until long after the initial brain
changes of PD are present. However, this is changing! There are two newly available laboratory tests that bring us closer to a new era in Parkinson’s diagnosis.
For more background, continue reading. If you’d like to skip down to learn about the two new lab tests for Parkinson’s, click here.
Why we need a biomarker for Parkinson’s disease
A biomarker is a measurable characteristic in the body that indicates that disease is present. A biomarker can be a lab test, an imaging test, or a clinical test. Common biomarkers include hemoglobin A1c for diabetes, or ejection fraction (calculated by an Echocardiogram) for heart failure. You can read more about the development of a biomarker for PD in a prior blog.
There are many reasons why a biomarker for PD is essential. First of all, having an accurate biomarker would be extremely helpful in clinical trials as it would ensure that everyone in the trial was diagnosed correctly. In addition, if the biomarker changed with disease severity, then it could be used to monitor whether the new drug being tested was effective or not.
An accurate biomarker would also be very helpful in the clinical setting. It is known that the cell loss of PD begins decades before motor symptoms develop and that often certain non-motor symptoms appear first. Therefore, scientists and clinicians are searching for ways to diagnose PD earlier. Diagnosing the disease earlier, with a biomarker, may allow people with PD to take measures to improve their health earlier, and may be an essential element to developing a neuroprotective medication, a drug that slows down or reverses the nerve damage of PD. It is possible that such a medication would only work at the earliest stages of the disease.
In addition, there are a number of neurologic syndromes that share features of PD. While neurologists are trained to differentiate between these syndromes, researchers are looking for ways to distinguish between different diagnostic possibilities more accurately.
There’s no consensus on a Parkinson’s biomarker, but that is changing
Two tests are now commercially available that bring us closer to a new era in PD diagnosis. Please note, neither test is yet fully FDA approved for the diagnosis of Parkinson’s disease, but both can already be ordered by physicians. There continues to be disagreement in the movement disorders field about the use of these tests for clinical purposes. Also note that most people with a clear neurologic history and evident motor symptoms of PD do not need a confirmatory test of their condition. Talk with your doctor about your specific situation and whether either of these tests would be helpful for you.
Two New Laboratory Tests to Detect Parkinson’s Disease
SAAmplify-αSYN Test (previously called the SYNTap test)
The science behind the SAAmplify-αSYN test for Parkinson’s:
Many researchers believe that what underlies the development of PD is the misfolding of a normal protein called alpha-synuclein. Evidence suggests that misfolded molecules of alpha-synuclein can induce their neighbors to misfold, causing a cascade that eventually leads to aggregation or accumulation of abnormal alpha-synuclein. Clumps of misfolded alpha-synuclein build up in the brain and interfere with the normal functioning of the brain cells, eventually causing cell death. The process of misfolding is believed to start years or even decades before the appearance of clinical symptoms of PD.
Interestingly, these misfolded proteins are not only found in the brain, but can also be found in body fluids such as cerebrospinal fluid (CSF) and blood, before clinical symptoms develop, and therefore may be able to be used as biomarkers for early diagnosis of these diseases.
However, the quantities of these abnormal protein collections present in body fluids are very low. Therefore, new methods needed to be invented to detect them effectively and reliably. A test called the Seed Amplification Assay (SAA) has been developed to detect abnormal aggregates of alpha-synuclein. Of note, this approach is very similar to other assays known by the names of Protein Misfolding Cyclic Amplification (PMCA) and Real-time Quaking Induced Conversion (RT-QuICR).
In the SAA test, a sample of either blood or CSF, that may or may not contain misfolded proteins, is mixed with normal proteins in defined experimental conditions. The very small amount of misfolded protein in the patient’s sample can act as a seed, triggering normally folded protein particles to misfold and aggregate in an amplification process. Once the amount of misfolded protein reaches a certain threshold, it can be detected using a fluorescent probe.
SAA has been developed to reliably detect abnormal alpha-synuclein in CSF. This test is now commercially available and can be ordered by a physician. There is more misfolded protein in CSF than in blood, which makes it easier to use for detection. However, collection of CSF is more invasive than a blood test (CSF samples are obtained via a needle inserted into the fluid surrounding the spinal nerves that emerge from the bottom of the spinal cord). Research continues to try to adapt this test to be performed on blood. APDA is on the forefront of these efforts, funding Dr. Mohammad Shahnawaz in his research to develop an SAA test for PD on a blood sample.
In 2019, the company Amprion received Food and Drug Administration (FDA) “breakthrough device designation” to introduce SAA as a test to detect Parkinson’s disease early.
This special FDA designation is given to medical devices with the following qualifications:
- It provides effective diagnosis of life-threatening or irreversibly debilitating human diseases or conditions.
- It offers a service when no approved or cleared alternatives exist.
- It represents significant advantages over approved alternatives, and/or its availability is in the best interest of the patients.
This special designation accelerated the development of Amprion’s SAAmplify-αSYN and gave it priority for review at the FDA. This designation allowed Amprion to offer the test commercially before full FDA approval and in October 2021, Amprion announced the commercial rollout of the SAAmplify-αSYN. The company is in the process of getting full FDA approval (beyond the breakthrough device designation) but it is currently available for your doctor to order.
Studies have determined that the test is 87% sensitive (which means out of 100 people with the PD, 87 will test positive using this test – the rest will have a false negative result) and 97% specific (which means out of 100 without PD, 97 will test negative – the rest will have a false positive result). The test has an accuracy of 94% (which means that out of 100 people in the population, 94 will receive a correct result – either positive or negative).
To receive the test, your doctor will either collect the CSF sample in his/her office or send you to a facility for collection of the fluid. The sample is then shipped to Amprion, who completes the test within two weeks and sends a report back to your doctor about whether misfolded alpha-synuclein is present in the CSF or not. Your doctor will then discuss the results with you. Currently, the test is self-pay (meaning insurance does not cover the cost of the test) and costs $1,500. The company states that they have financial assistance programs for those who are eligible, and they are working to establish reimbursement from Medicare, Medicaid, and private insurance providers.
The test can distinguish whether or not misfolded alpha-synuclein is present, but it cannot distinguish between Parkinson’s disease, Dementia with Lewy bodies, and Multiple System Atrophy – all of which have misfolded alpha-synuclein present – so it will be up to your neurologist to differentiate between these conditions based on the clinical information available.
The Syn-One Test
The science behind the Syn-One test, a skin test for Parkinson’s:
Research has demonstrated that phosphorylation, or the attachment of a phosphate group, onto the alpha-synuclein molecule can result in a particularly harmful form of alpha-synuclein. Phosphorylated alpha-synuclein can be found in nerves all over the body of a person with PD including in nerve fibers of the skin. These nerves can be accessed for study in a lab via a skin biopsy. CND Life Sciences developed the Syn-One Test to detect the phosphorylated form of alpha-synuclein in series of skin biopsies as a way of diagnosing disease.
Your neurologist will perform the skin biopsies or possibly refer you to another physician to perform the test. The skin is numbed with a local anesthetic and the biopsies are taken from three locations – the upper back, the lower thigh, and the lower leg. The samples are then shipped to CND Life Sciences for analysis and the results are returned in 2-3 weeks.
CND Life Sciences reports that the Syn-One Test has a sensitivity of 95% and a specificity of 99% on their internal tests, although this data is not published yet in a peer reviewed journal. Studies from other laboratories investigating the presence of phosphorylated alpha-synuclein in the skin of people with PD report more variability. The variation in results can likely be attributed to the variation in how the biopsy is performed and analyzed. This could include elements such as location of the biopsy, thickness of the biopsy and reagents used for detection, all of which CND has worked to optimize.
CND Life Sciences is currently conducting a clinical trial funded by the National Institutes of Health to validate the Syn-One Test in 300 subjects and 200 controls in 25 sites across the US. This additional data will ideally help them obtain full FDA approval for use as a diagnostic test for PD.
As with the SYNTap test, Syn-One is not able to distinguish between different diseases in which phosphorylated alpha-synuclein accumulates including Parkinson’s disease, Dementia with Lewy bodies, and Multiple System Atrophy, but it is able to distinguish between these diseases and those that do not harbor phosphorylated alpha-synuclein. Your neurologist will further refine your diagnosis based on your clinical features.
Although the company does not yet have FDA approval as a diagnostic test for PD, the test is available as a pathologic test that determines whether a tissue sample contains phosphorylated alpha-synuclein and can be billed through Medicare.
The company also has contracts with some private insurance providers, and they are working to expand this to include more insurance providers.
The development of these tests is an exciting advancement for the PD community. We look forward to additional testing possibilities that will provide physicians with better tools to diagnose Parkinson’s disease more accurately and efficiently.
Tips and Takeaways
- Two new laboratory tests are commercially available for doctors to aid in the diagnosis of PD. Both tests have their limitations and movement disorders physicians continue to use the clinical exam as the gold standard for PD diagnosis
- One test is performed on a sample of cerebral spinal fluid and the other on a set of skin biopsies
- Talk with your doctor about your specific situation and whether either of these tests would be helpful for you