ASU, Mayo research collaboration seeks early diagnosis for Parkinson's

In 1999, when Americans watched as Michael J. Fox — beloved to many as the smooth, wisecracking Marty McFly — swayed and shifted uncontrollably, clenching and unclenching his fists as he provided solemn testimony to the U.S. Senate Appropriations Subcommittee on the realities of life with Parkinson’s, it drew attention to a disease that affects nearly 1 million people in the U.S. and nearly 5 million worldwide.

Like many neurological disorders, Parkinson’s disease, or PD, is characterized by the slow degeneration of physical and mental functions that only present once it has progressed beyond the point where medical intervention can do anything to stop it. And although there are treatments for the symptoms, they become much less effective the more advanced PD is when they are first administered, making early diagnosis crucial to quality of life. 

But how do you diagnose a disease before it displays observable signs?

A Mayo Clinic neurologist and an Arizona State University professor — Dr. Charles Adler and Michael Sierks, respectively — are hoping to identify blood-based biomarkers for Parkinson’s that would allow for earlier, more accurate diagnoses, the ability to track the progression of the disease and more targeted treatment options. The pair’s ongoing research was initially facilitated by the Mayo Clinic and ASU Alliance for Health Care’s Faculty Summer Residency Program.

The program is designed to support long-term collaborations between research teams at Mayo Clinic and ASU faculty in areas that will impact clinical outcomes and enhance patient experiences. Other researchers in this year’s cohort are also working side by side to transform scientific discoveries into breakthrough therapies and critical advances in patient care.

Adler and Sierks both have a family history of neurodegenerative diseases (Adler’s grandfather had Parkinson’s, and Sierks’ father has Alzheimer’s).

“I always wanted to be a doctor and I always wanted to cure PD, so for me this has been a lifelong journey,” Adler said.

The cause of Parkinson’s isn’t clear, but what is known is that it results in the gradual breakdown of dopamine nerve cells, which leads to such motor issues as resting tremors, slowness of movement, rigidity and difficulty with gait, as well as such non-motor issues as drops in blood pressure, constipation and loss of the sense of smell.

Though a person can live with it for decades, the most pressing issue is maintaining quality of life.

“The scary part” about PD, Sierks said, “is that by the time Dr. Adler diagnoses somebody with it, about 60 to 80 percent of their dopamine nerve cells have already been lost. So trying to fix the problem after diagnosis is really hard, because there’s so much damage already.”

Identifying a biomarker for early-stage PD could help to mitigate that damage.

Using biomarkers to diagnose medical conditions is nothing new. Blood pressure, temperature and pulse rate are all biomarkers that can tell doctors what’s going on in a patient’s body.

In order for a biomarker to determine for sure whether an individual will get Parkinson’s, one must be identified that is both sensitive to PD, meaning that every or almost all PD patients have it, and specific to PD, meaning that the biomarker is only found in cases of PD and not in other diseases.

One biomarker that is known to be indicative of Parkinson’s is the protein known as alpha synuclein. The challenge with testing patients for synuclein is that it is a normally occurring protein in the body, and even has beneficial functions.

However, Sierks’ has found that there are certain abnormal forms of synuclein that arise when the cells that create the protein become stressed and malfunction — which can be caused by normal, everyday stressors, substance abuse or environmental factors.

“Cells misproduce proteins all the time,” Sierks said. “And it’s all a balancing act. They generate good proteins, they generate bad proteins. As long as they can clear the bad proteins faster than they generate them, everything’s fine. I like to use a garbage-truck analogy: As long as your garbage truck is bigger than the garbage you’re generating, cells are happy. But as you get older, your garbage truck gets smaller and your garbage increases. At some point, the balance starts to shift and you start generating more bad stuff.”

Those abnormal forms of synuclein are both sensitive and specific to Parkinson’s, but they vary depending on the stage of the disease. Researchers know which forms are indicative of the mid- to late-stages of PD because they were able to analyze samples from patients in those stages and identify them. However, researchers still don’t know the precise abnormal form of synuclein that is indicative of early-stage PD because patient samples of that stage are so hard to come by.

But there are some ways to obtain them. One way is to recruit individuals who carry the gene for Parkinson’s that puts them at a high risk for developing it and periodically take blood samples from them over time. Later, samples that were taken from the individuals who did develop PD at a point in time before they displayed outward symptoms can be used to identify biomarkers of the earliest stages of the disease.

Another way is to take biological samples from individuals who have donated their bodies to science and were found upon autopsy to have indicators that they may have developed Parkinson’s had they lived longer.

With those samples, Sierks hopes to identify the precise abnormal form of synuclein that indicates early-stage PD so that doctors can begin testing for it.

“My goal is that this would just become another one of the routine blood exams performed once you get to adulthood,” he said.

Sierks — who is affiliated with both the School for Engineering of Matter, Transport and Energy and the School of Life Sciences at ASU — has had success identifying biomarkers that have been used to diagnose Alzheimer’s as early as five to 10 years before an initial diagnosis of mild cognitive impairment, and he believes the same is possible for Parkinson’s.

Both he and Adler are grateful for the funding and time the Mayo Clinic and ASU residency has afforded them to work on this research, for which they are currently applying for additional funding and expect to span the rest of their careers.

“Research drives everything we do for our patients. Having Mayo Clinic and ASU underwrite these type of collaborations supports one of our most important research missions — improving the care and quality of life of our patients,” said Dr. Adler.

“By integrating the rich expertise of our ASU colleagues, together we can accelerate the discovery, development and application of life-changing therapies so that our patients receive exactly the care they need.”

Top photo: Mayo neurologist Charles Adler (left) and ASU Professor Michael Sierks in Adler's exam room at Mayo Clinic in Scottsdale. Photo by Charlie Leight/ASU Now