Our study on misfolded Synuclein has advanced Parkinson’s diagnosis research, giving birth to a new test for doctors to diagnose the disease early. How early? Decades before the patient shows movement disorders.
Early diagnosis of Parkinson’s Disease (PD) gives people a better quality of life and allows the doctor to formulate treatment options. The key is to delay or stop the progress. This blog shows the major discoveries on detecting alpha-synuclein (aSyn), a biomarker for PD, published in Nature (February 2020) and highlighted in NIH Research Matters.
As the developer of Protein Misfolding Cyclic Amplification (PMCA) technology and on behalf of the team at UTHealth, I’d like to thank The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and the National Institute on Aging (NIA) for jointly funding this Parkinson’s Diagnosis Research.
We’ve discovered some major applications to advance the early diagnosis of PD and other neurodegenerative diseases such as Alzheimer’s. I’ll cover the key topics for Parkinson’s, the problems with detecting PD currently, the solutions (and hope) our research brings to early testing for PD.
What is Parkinson’s Disease?
Parkinson’s Disease is a chronic, progressive brain disorder representing the most common neurodegenerative illness after Alzheimer’s.
PD causes a person to lose control over some bodily functions. Usually, Parkinson’s affects older people, but it also happens at any age. Early signs of Parkinson’s include the following:
- Tremors of the hands,
- Slow movements,
- Muscle stiffness,
- Impaired posture,
- Trouble sleeping,
- Depression or mood changes
- Constipation
- Loss of smell, balance, voluntary movements, and speech changes.
Here is a good resource to learn more about Parkinson’s, such as what to expect and other early signs or symptoms of Parkinson’s WebMD Parkinson’s Slideshow
How Parkinson’s Disease Affects People?
About 1 million people in the U.S. and 10 million worldwide are affected by Parkinson’s Disease. Each year, about 60,000 people in the U.S. learn they have Parkinson’s.
Both females and males get Parkinson’s Disease; however, it’s 1.5 times more common in men.
It is also more common in older folks, although 4% of the cases happen in people under 50.
Causes Of Parkinson’s
According to the American Parkinson Disease Association, there may be more than one cause. However, there is evidence for the role of genetics, environmental factors, or a combination of both.
On the cellular level, Parkinson’s is brought on by the death of nerve cells in the substantia nigra, a brain region that controls movements.
Parkinson’s Disease
This cell death appears to be caused by the progressive accumulation of protein aggregates in the brain. These aggregates are composed of the protein alpha-synuclein, which becomes misfolded and acquires the ability to spread the damage from cell-to-cell similarly to a prion. The larger aggregates of synuclein observed under the microscope in Parkinson’s patients are called Lewy Bodies.
These aggregates form in the patient’s brain for years or decades before any clinical symptoms appear. Misfolded proteins spread slowly but persistently, destroying the brain without being detected by conventional methods.
The Lack Of Treatments For Parkinson’s Disease
Currently, there is no treatment to stop Parkinson’s progression. Many drugs aimed to stop brain diseases have failed in clinical studies because it is challenging to cure the brain after severe damage. The critical challenge here is the lack of a biochemical test before the patient shows clinical symptoms. So this begs our next question.
How Is Parkinson’s Diagnosed Currently?
At the moment, patients can be diagnosed with Parkinson’s only after they show clear disease symptoms. But what happens to the brain at the point of diagnosis?
Well, it turns out more than 50% of the patient’s nerve cells in the substantia nigra have already died by then. As a result, the brain is unable to regenerate.
These brain cells, once they are dead, they are dead forever. Therefore, the brain’s destruction leads to major and incurable consequences, such as the case in Parkinson’s.
Solutions From Our Parkinson’s Diagnosis Research
As the chief scientific officer at Amprion, we apply the PMCA (also known as RT-QuIC) technology on a commercial scale for accurate, early testing for Parkinson’s and various brain diseases.
Our goal is to offer people molecular-based early diagnosis for Parkinson’s, way before any clinical symptoms appear, and minimal damage to the brain.
How Does PMCA Work?
The PMCA technology mimics and measures the abnormal process of protein misfolding and aggregation in the brain accelerated through an amplification process in the laboratory. This amplification technology makes the disease biomarkers easily detectable.
Why Do People Test For Parkinson’s When There’s No Cure Yet?
To treat the disease, we have to know the condition exists first.
Without an accurate diagnosis of Parkinson’s Disease at the early stages, science and medicine have been working blind for more than 100 years to develop treatments.
Successful implementation of early testing for Parkinson’s Disease will bring significant changes, from accelerating drug developments in finding a cure to benefiting people in proactively managing their life journey in delaying or preventing the onset of symptoms through lifestyle changes, healthier diets, and exercise programs, etc.
Early diagnosis of Parkinson’s also allows your doctors to steer you on the right course of suitable treatment options early when the brain is healthier and more likely to respond to intervention.
As early testing for Parkinson’s is widely adopted, we also empower scientists with critical data to advance research, such as analyzing how Parkinson’s Disease progresses in the brain and developing effective treatment pathways to slow or even prevent the onset of Parkinson’s symptoms.
This, in turn, enables us to work with pharmaceutical companies to recruit suitable patients for the right drugs and the proper clinical trial, monitor the treatments’ efficacy, and develop personalized medicine. Ultimately, together we will find a cure for Parkinson’s Disease.
Below are brain images comparing a PD patient’s brain from healthy to pre-symptomatic to post-symptomatic stages. The key to treating any disease is to know it’s there and as early as possible to start preventive care. The goal is to delay or stop the progression.
Interestingly, we can also apply the same biomarker detection science for Alzheimer’s testing using blood.
The accumulation of protein aggregates is not unique to Parkinson’s. It also causes other incurable illnesses: Alzheimer’s, frontotemporal dementia, amyotrophic lateral sclerosis, Dementia with Lewy Bodies (DLB), Huntington’s disease, and countless others.
These diseases are associated with accumulating a different protein in distinct organs, but the process is very similar.
Amprion is extending the PMCA technology for early diagnosis of Alzheimer’s Disease, offering testing for Alzheimer’s at early stages. Through early diagnosis, we enable therapeutic intervention to delay or prevent the onset of Alzheimer’s symptoms.
We focus on bringing the best possible quality of life to people at risk of Parkinson’s and Alzheimer’s Diseases. The only way to achieve this goal is through early testing of these neurodegenerative diseases.
Our group of scientists is working towards a singular vision: A world without Parkinson’s, Alzheimer’s, diabetes, or cancer.
The key is detecting these deadly diseases at the earliest stages and applying the proper treatments before they destroy our lives. Early testing is the key to finding a cure for incurable diseases like Parkinson’s and Alzheimer’s.
When Will The Tests Be Ready For Parkinson’s or Alzheimer’s?
The FDA awarded Amprion Breakthrough Device Designation for the detection of synuclein in May 2019. And we’ve been working hard to scale up our assay for commercial use to meet CLIA and FDA approvals.
We’re excited that our SYNTap Biomarker Test®️ is now commercially available. And our CLIA certified lab is accepting CSF samples from physicians.
How Early Is Early Testing?
Using our biomarker-testing, we’re talking about giving people the ability to find out, with certainty, whether they have Parkinson’s or Alzheimer’s decades before they show any clinical symptoms. This is what we believe in—Early.
Early means developmental stages. Early leads to prevention and eventually finding the cure for Parkinson’s, Alzheimer’s, and other incurable diseases.
Other Implications: Detecting Multiple System Atrophy (MSA).
Our latest study recently published in Nature showed that PMCA technology could identify Parkinson’s patients. It also allows us to distinguish Parkinson’s from a clinically similar disease, known as multiple system atrophy (MSA).
The accumulation of alpha-synuclein aggregates causes both PD and MSA, but each of these diseases affect different nerve cells.
Even though both diseases may initially show similar clinical symptoms, making it difficult for doctors to diagnose accurately, these diseases progress very differently, requiring distinct treatments. Thus, it is critical to establish an early testing procedure to effectively identify which disease affects the patient.
Our study demonstrated that even though these aggregates’ protein component is the same in both diseases, the aggregates’ shape is different.
The PMCA assay detects the specific shape of the proteins, enabling doctors to diagnose the disease accurately. The study unveils many implications for Parkinson’s Disease diagnosis.
I hope this article helps you better understand our research and how our work brings hope in early testing for Parkinson’s, Alzheimer’s, MSA, and other prion diseases.
Read the article published in Nature (February 2020).
Learn more about our SYNTap Biomarker Test®️ to help doctors diagnose PD accurately.
Claudio Soto, Ph.D., is a professor in the Department of Neurology at McGovern Medical School at UTHealth. He also serves as the chief scientific officer at Amprion. The company is gearing up for the commercial rollout of early testing for Alzheimer’s and Parkinson’s.
