In August’s Live Well Today webinar, neurologist Alberto Espay, MD, discussed Parkinson’s subtypes, why they are important, and what they mean for people living with Parkinson’s today.
You can watch or listen to the webinar below. Subscribe to our YouTube page so you can be notified whenever we upload new content.
SHOW NOTES
PARKINSON’S IS PERSONAL
No two people with Parkinson’s experience it the same way. Motor symptoms vary. Non-motor symptoms vary. The age of Parkinson’s onset and diagnosis varies. The rate of progression varies. In other words, as Dr. Espay said in the webinar conversation: “There isn’t a pre-established script that Parkinson’s follows.”
All of these variations in Parkinson’s can be referred to as phenotypes. Due to the diverse phenotypes of Parkinson’s, many Parkinson’s researchers, experts, and movement disorder specialists—Dr. Espay among them—consider Parkinson’s to be more than one condition.
Subtyping addresses this. It centers around the premise that everyone living with Parkinson’s is different, living with Parkinson’s that is unique to them. It also recognizes that there are many different root causes of Parkinson’s, rather than a single cause.
And, because there are many different root causes of Parkinson’s, there can be no one single “cure” for Parkinson’s, as Dr. Espay explains. What may slow, stop, or reverse Parkinson’s progression for one subtype may have no effect on the progression of Parkinson’s among those with another subtype. Many different disease-modifying therapies need to be discovered, because there are many different subtypes of Parkinson’s.
Dr. Espay explained that knowing about Parkinson’s subtypes—and knowing which subtype of Parkinson’s you are living with today—is important for two key reasons: First, this knowledge can help you make decisions about your current treatment and approach to living well. You can dig into research about the subtype of Parkinson’s you have and learn about specific medication recommendations and intervention strategies focused on that subtype.
Second, understanding your subtype can help you explore the ongoing clinical trials that investigate aspects of your subtype. As experts continue to build understanding of Parkinson’s subtypes, they help expedite the drug development process by ensuring that the people most likely to benefit from any particular treatment are well-represented in clinical trials.
PARKINSON’S SUBTYPES AND PARKINSONISM
Six of the most common ways clinicians and research have historically attempted to subtype Parkinson’s are to differentiate–
- Between Parkinson’s and other types of Parkinsonism
- By the age of Parkinson’s onset
- By whether or not there is a genetic variant/family history
- By which symptoms are most prominent
- By whether a person’s Parkinson’s began in the gut or the brain
- By severity and variety of symptoms
During this webinar Dr. Espay suggests that the usefulness of these groupings is generally limited because, at present, we don’t understand the underlying biology of each of these groups very well. One exception Dr. Espay discusses is that we know there are genetic variants that can cause Parkinson’s, but it is important to know that each gene can vary in different ways.
GENETICS AND PARKINSON’S
Of the main subtypes, Dr. Espay focused most on the genetically driven forms of Parkinson’s because these subtypes are the ones we have the most concrete biological data about. Researchers have discovered more than 20 genes that cause Parkinson’s, and there are other genes that increase the risk that a person will develop Parkinson’s.
Dr. Espay said that–in general–people who experience Parkinson’s at an earlier age (typically age 50 or younger) are likelier to have a genetic risk factor or cause. He also said people with fewer non-motor symptoms are more likely to fall into a genetic subtype.
Subtyping by genetics helps in the development of treatments that target certain genes–those genes that have been shown to play a role in Parkinson’s onset. Dr. Espay discussed how people with the genetic Parkinson’s subtype are more likely to respond to therapies that specifically address the genetic cause of their Parkinson’s. It is also true, however, that there are multiple variants possible in any specific gene. Because of this, it is not necessarily the case that if you have a genetic variant in a specific gene any treatment targeting that gene will work well for you. There may, in other words, be subtypes even of subtypes.
If you’re not sure whether your Parkinson’s is genetically caused, you can explore getting a genetic test. There are pros and cons to genetic testing, so discuss the option with your care team. A genetic counselor can help you understand how genetic testing works, what you might learn from testing, and what you might do with what you learn.
THE BIOMARKER Question
There has been much excitement in the Parkinson’s news space recently about biomarkers and tests that can confirm Parkinson’s. Dr. Espay took a deep dive into the headlines and the science behind them during a discussion about alpha-synuclein.
Alpha-synuclein is one of three types of synuclein and is a small protein found abundantly in the brain and also present in the heart, muscle, and other bodily tissues. For years, alpha-synuclein has been thought by many Parkinson’s experts to be the primary cause of Parkinson’s because it clumps together (or aggregates) into Lewy bodies in the brain. These clumps of alpha-synuclein are thought to cause the neuronal damage associated with Parkinson’s.
Dr. Espay explained that this is not as cut and dry as it sounds. Synuclein, he explained, is found throughout people’s bodies and helps us survive in numerous ways. Also, while most people’s Parkinson’s is related to synuclein, Dr. Espay says that Parkinson’s is, from his perspective, not caused by synuclein. For people with Parkinson’s, something biological is driving the buildup of misfolded alpha-synuclein, and it’s the “something biological” that needs to be identified.
For similar reasons, Dr. Espay cautioned the audience about anti-protein therapy trials, saying that “anti-protein therapies just can’t work because proteins are not the cause of the problem in Parkinson’s or any disease of aging.”
Dr. Espay’s Views of the “Biomarker Breakthrough”
You may recall the biomarker news that made headlines in 2023. The test associated with that news examines alpha-synuclein.
Discussing this news, Dr. Espay said the Syn-Tap is a qualitative test that can confirm whether or not there are misfolded clumps of alpha-synuclein in a person’s cerebrospinal fluid. He said that what this test does well is confirm a Parkinson’s diagnosis for someone who is experiencing symptoms of Parkinson’s. However, he said, “It’s not going to add anything to that. It’s going to tell you that your Parkinson’s is related to synuclein, but most people’s Parkinson’s is related to synuclein. Not caused by synuclein; related to it.”
What this biomarker test cannot do is the very thing Dr. Espay says is key to finding cures for Parkinson’s. The test cannot define a person’s biological cause of Parkinson’s, he explained. It cannot tell experts about the severity of someone’s Parkinson’s, or whether the Parkinson’s is primarily motor or non-motor. Given these limitations, the 2023 biomarker news was another example, from Dr. Espay’s perspective, of why it is important to think critically about all flashy headlines.
CCBP AND PRECISION MEDICINE
Discovering the biological cause of a person’s Parkinson’s is central to Dr. Espay’s work. “We need to get to know people with Parkinson’s at a biological level, to understand what Parkinson’s is for you,” he said. “We want to know as much as possible what the source of your Parkinson’s is to know best how to treat your Parkinson’s.”
And, he says, this can only be done in an individualized fashion.
The Cincinnati Cohort Biomarker Program (CCBP) is doing exactly this. The study centers around precision medicine and matching a person’s biological phenotype to their Parkinson’s treatment. It recognizes the individuality of everyone in the study. “We’re looking at people from the biological viewpoint, not from their symptoms,” Dr. Espay said.
The goal of the study is to match people with therapies that can change their Parkinson’s for the better and, ideally, even reverse their Parkinson’s.
“We may already have on our pharmacy shelves therapies that could work to reverse Parkinson’s for many people. We just don’t know who they are, biologically. This is what the CCBP is about–knowing who the people with Parkinson’s are biologically, and finding the therapies for them based on the biological causes of their Parkinson’s,” Dr. Espay explained.
In its first phase, the CCBP will recruit 5000 people into one study. Each participant will visit the Parkinson’s clinic at the University of Cincinnati to undergo examinations and have blood, urine, and stool samples collected. The research team will analyze the data collected and “let the biology tell us how to group people together, as well as which markers we might be able to target,” the study site says.” Once we have these subtype specific markers of disease, we can then start to match them to existing therapies.”
You can learn more about the study here.
THE QUEST FOR CURES for PARKINSON’s
The fact that subtyping of Parkinson’s is possible means that there can be no single cure for Parkinson’s. There need to be many cures, Dr. Espay said, because “what’s going to cure Mary’s Parkinson’s won’t be what’s going to cure Jim’s Parkinson’s.”
As experts like Dr. Espay continue to learn more about subtypes and their biological causes, they are making progress toward discovering these cures. In the meantime, he says, the important thing for people with Parkinson’s is “to recognize you are your own subtype. Believe that Parkinson’s isn’t going to define you, that Parkinson’s isn’t going to dictate what you can do or can’t do. You’re blazing your own trail. So make the best of that trail.”
ADDITIONAL RESOURCES
Cincinnati Cohort Biomarker Program: More Details
Parkinson’s Subtypes: Heterogeneity, Prognosis, and Treatment Development
Atypical Parkinson’s: What is Multiple System Atrophy?
DaTscan: What It Is, How It Works, and What It Can Tell You
Clinical Trials for Parkinson’s: A Primer
Speaker Bio
Alberto Espay, MD
Alberto J. Espay, MD, is a movement disorder specialist who practices at the University of Cincinnati’s Gardner Center for Parkinson’s Disease and Movement Disorders. Dr. Espay currently serves as chair of the Pan American Section of the International Parkinson and Movement Disorders Society (MDS-PAS), and he has published over 350 peer-reviewed articles and 40 book chapters. He has also written 10 books, including “Brain Fables,” which he co-authored with Benjamin Stecher, a person living with Parkinson’s. Dr. Espay is an active researcher and leads the Cincinnati Cohort Biomarker Program, which aims to separate neurodegenerative diseases into their proper biological subtypes and then match each one to therapies that will be able to alter disease progression.
Our Live Well Today Webinar Series is supported by our Peak Partners.
