Through MJFF’s Parkinson’s Progression Markers Initiative (PPMI) study, researchers validated a test that can, with high accuracy, identify Parkinson’s proteins in the spinal fluid. (Read the full results in Lancet Neurology.) The test, known as an alpha-synuclein seed amplification assay (αSyn-SAA), has immediate — and wide-ranging — research implications. It will transform how trials are done, potentially decrease time to new treatments and move the field a step closer to preventing Parkinson’s disease (PD).
But how does it impact care? While αSyn-SAA is now available through a doctor’s office, it doesn’t yet broadly change how doctors diagnose and treat PD. But it likely will in the future. That’s because the test measures the biology of Parkinson’s disease. For the first time, it allows us to look at what’s happening inside the body to explain the various symptoms and experiences of PD and related disorders.
To learn more about the test, who might consider it, and what it may mean for Parkinson’s care, we spoke with Un Jung Kang, MD, a movement disorder specialist, researcher and Founders Professor of Neurology at NYU Grossman School of Medicine in New York City, who has been working on αSyn-SAA through MJFF-sponsored BioFIND and PPMI biomarker studies.
The Michael J. Fox Foundation (MJFF): Tell us briefly about the test.
Un Jung Kang (UK): αSyn-SAA looks for an abnormal form of alpha-synuclein protein in spinal fluid. This abnormal protein is seen at autopsy, in the brains of most people with Parkinson’s disease and related disorders of alpha-synuclein, such as Dementia with Lewy Bodies (DLB) or Multiple System Atrophy (MSA). (Read about these atypical parkinsonisms.)
MJFF: What can the test tell and not tell?
UK: The test can tell whether you have abnormal alpha-synuclein at the time it’s done. And it can do this very accurately. The result is yes or no — you have the abnormal protein, or you don’t. The current form of the test can’t tell how much you have or if and how that’s changing over time.
Like many tests, the results have to be put in the context of your medical history and symptoms to understand what, exactly, they might mean.
MJFF: Can it diagnose Parkinson’s?
UK: On its own, no. For example, it can be positive in people who have DLB or MSA. It also may be positive in some people who have these conditions but have not yet developed symptoms and, rarely, in people without disease.
And the test doesn’t replace how doctors diagnose Parkinson’s disease. Today, a diagnosis is made when a person has “cardinal” motor symptoms — slowness plus tremor or stiffness. And that’s not changing yet. But αSyn-SAA could be a helpful addition to a doctor’s examination, especially if there is a question or a person wants to feel more confident in their diagnosis.
It’s important to note that the test may not be positive in everyone who has Parkinson’s disease as we know and define it today. In studies, people diagnosed with PD who have a LRRK2 genetic mutation are less likely to have a positive αSyn-SAA test than those with Parkinson’s who do not have the genetic mutation. That doesn’t change their diagnosis or the symptomatic treatments we currently use. It does, however, tell us more about the biology of their disease — they may be less likely to have abnormal alpha-synuclein. And that could have huge implications for disease understanding, research and, in the future, more precise Parkinson’s therapies targeting underlying biological processes.
MJFF: Does this change how we care for Parkinson’s?
UK: Not yet, but it likely will. This test adds significantly to what we know. It gives better insight into what’s happening in the body and in the cells with PD — it moves beyond what we can see with just symptoms. Historically, we’ve lumped Parkinson’s into one basket. But everyone with the disease is different — different symptoms, different rates of progression.
If we say Parkinson’s is an “apple,” now we can start to see the color. Most might be red, but some are yellow, others are green, and still others are red and green. We treat every apple the same way now, but we may, in the future, be able to use different, more personalized approaches depending on the color of the apple.
MJFF: Should people living with Parkinson’s get this test?
UK: As doctors, whenever we think about doing a test, we ask: Will this change how I medically treat the person? Will it give information about the future? If the test might help inform how we and our patients act, then it’s worth doing. If not, it may not be worth the risk, your time, or any expenses to you.
For people living with Parkinson’s, especially if it’s been a few years or more since diagnosis, and there are typical symptoms or good medication response, the test may not be necessary. It won’t change which currently available treatments we use, and it doesn’t tell the extent or expected progression of disease. It may however identify that this person is eligible for a specific clinical trial, and many clinical trials may soon require this test.
In some people, especially early on, a PD diagnosis might be a little less certain or clear. Rather than wait and see, some would rather confirm “bad news” than live with “unclear news.” Many also share they want something more tangible and objective, in addition to an expert diagnosis based on opening and closing your fist, tapping your feet and walking down the hall. In these cases, the test may help.
Whether and when to get the test is a personal decision best made with your movement disorder specialist.
MJFF: What about people who are at risk for Parkinson’s — should they get the test?
UK: One of the major, more recent developments in the PD field is that we can recognize some symptoms that can precede motor symptoms — tremor, slowness and stiffness — that are currently the basis of a Parkinson’s diagnosis. People with REM sleep behavior disorder (RBD), for example, which involves acting out dreams, have a high likelihood of developing PD after years or decades. And recent studies show that αSyn-SAA is positive in a high percentage of those with RBD. Whether you want to know if your alpha-synuclein is abnormal at this stage, when you do not have PD motor symptoms and we do not yet have a treatment that slows the disease, is an individual preference. Some people want to know as much as they can — it’s empowering. Others feel better without information that could bring anxiety and worry about the future.
All these considerations will change when we have therapies to prevent and slow the disease.
MJFF: How is this test done?
UK: The test is available through your doctor. If you’re considering it, I’d strongly recommend you see a movement disorder specialist, a Parkinson’s expert, to learn more and discuss what the test can and can’t tell you. (Find a movement disorder specialist near you.) I can’t stress enough that whether to get the test depends on you: what you’re comfortable with, what your situation is, whether the results would change medical management or life perspective, and more. This is why it must be done only after thorough discussion with your doctor.
The test requires a spinal tap, or lumbar puncture. While it sounds scary, it’s a commonly performed and relatively benign procedure. Your doctor inserts a needle between the vertebrae (bones) of your spine, below your spinal cord, to remove a small amount of spinal fluid. (This is quickly replenished.) Risks are extremely low and include infection, bleeding and temporary headache.
MJFF: How much does the test cost?
UK: The test itself is not yet covered by insurance and each person’s out-of-pocket costs vary. And there may be additional costs related to the doctor visit and lumbar puncture procedure. Speak with your provider, insurer and the company that runs the test to learn about estimated costs.
MJFF: What are the next steps for this test?
UK: The assay is very accurate and it’s ready now to help improve clinical trials — first, to ensure we include people with abnormal alpha-synuclein in trials testing therapies against alpha-synuclein to slow disease. There are at least a dozen of these trials underway. And when we have treatments to slow or delay disease onset, we can also test them in people who have RBD and other early potential signs of PD to, hopefully, prevent the disease from ever coming on.
The next steps for αSyn-SAA are to:
- Create a similar test for blood, skin, nasal swab, or other tissues or body fluids that are more easily accessible.
- Fine tune the test so that it can distinguish PD from similar diseases, like MSA, more precisely. Early research suggests it might separate these conditions, but more work is necessary.
- Quantify results — move from a yes-no to a measurable result and see if and how results change over time and correlate with symptoms, disease progression and treatment impact.
MJFF: Many people ask about the DaT brain scan for Parkinson’s. How is this test similar or different?
UK: DaTscan and αSyn-SAA are both very accurate tests, but they tell different things. DaTscan is a specialized brain imaging scan that shows loss of dopamine — a brain chemical. It can help separate Parkinson’s from other conditions that cause similar symptoms but don’t involve dopamine, like essential tremor or vascular parkinsonism. But it can’t separate Parkinson’s from the atypical parkinsonisms, including DLB, MSA or Progressive Supranuclear Palsy (PSP). All of these conditions cause loss of dopamine, so all of them cause abnormal DaTscan.
αSyn-SAA, on the other hand, can tell us about the underlying biology of disease. Because it tests alpha-synuclein, it can separate conditions that impact this protein — PD, DLB, MSA — from those that don’t, like PSP. There are also some early indications that alpha-synuclein abnormalities may occur before the loss of dopamine detected by DaTscan. This might eventually help with diagnosis and research participation for those who do not have motor symptoms but are at risk for PD.
MJFF: What about the work to develop an alpha-synuclein brain scan? Is that no longer needed?
UK: It’s absolutely needed! These types of brain imaging scans aim to look at the same thing as the assay — alpha-synuclein. But they could show the anatomy and extent — where and how much protein is in the brain. This type of scan also might help us visualize how the protein changes over time — more with progression or less with treatment intervention. It’s a complementary tool that will help in both research and care.
Editor’s note: Read the latest on MJFF-funded work in this area.
MJFF: What’s the bottom line?
UK: αSyn-SAA, a validated biomarker for Parkinson’s, is one of the most dramatic advancements and important discoveries in the field. It’s almost like looking in the brain at a microscopic level. It gives us a whole new way of coming at the disease and treating the individual patient.
This demonstrates we’re making progress! But there’s, of course, still more work to do. To help this breakthrough continue to move forward, I’d encourage everyone to enroll in PPMI. Without the contributions of those who participated in these studies, we would not be where we are today.
Editor’s note: Learn more and join PPMI.
Dr. Kang serves on the scientific advisory board of Amprion, the company that developed the currently available alpha-synuclein seed amplification assay.