More than 200 coordinators, investigators, industry partners and patients gathered in New York City in early May for the annual Parkinson’s Progression Markers Initiative (PPMI) meeting. PPMI is our Foundation’s landmark study to better define and measure Parkinson’s disease (PD) to enable new treatments. The international study is following nearly 1,400 participants at 33 clinical sites with partnership from 26 industry groups. Each year representatives from across PPMI convene to discuss findings, challenges and future strategy.

“Our study has enormous resources that are widely used,” said principal investigator Ken Marek, MD, from the Institute for Neurodegenerative Disorders, in his opening remarks. “We continue to be flexible and grow the various assessments we are including in the study. We want to continue that strategy moving forward and take advantage of new advancements, technologies and capabilities that can enhance the cohort.”

Here we share some of the scientific findings, new initiatives and study updates shared at the 2019 PPMI Annual Meeting.

Scientific Findings

PPMI is producing greater understanding around the causes, onset and symptoms of Parkinson’s, leading to new ways to define, measure and treat the disease.

• Andy Singleton, PhD, from the National Institutes of Health and head of the PPMI Genetics Study Core, shared findings from work identifying Parkinson’s genetic risk factors. This information could point to new disease measures or treatment targets. “PPMI data is exquisite and far better than any other data in terms of depth and breadth and quality,” he said.
  • Analysis of data from PPMI and other studies has identified 90 genetic loci linked to Parkinson’s risk.
  • With some of these, Singleton’s team can create a genetic risk score based on how many mutations one carries and the strength of the mutations’ link to PD. People with the highest genetic risk scores are about six times as likely to have PD than people in lowest risk score category, Singleton reported.
  • PPMI scientists also are looking at what genetic mutations work together and how they modify one another. Initial results show changes in the CTSB gene, for example, may have a greater impact on patients with a GBA mutation.
• Daniel Weintraub, MD, from the University of Pennsylvania and chair of the PPMI Cognitive/Behavioral Working Group, reported on mood and thinking symptoms among study participants. This data can help understand disease progression.
  • Scores on cognitive tests do not decline much in the first five years with disease, and dementia is uncommon. However, depression and apathy increase over time.
• Lana Chahine, MD, from the University of Pittsburgh and chair of the PPMI Recruitment and Retention Working Group, discussed how many people in at-risk groups, such as people who carry genes that increase risk for PD, have converted to Parkinson’s since joining the study. Looking at biology and symptoms over time in those people can help point to early measures or markers of disease that could lead to better diagnostics or even preventive treatments.
  • There are a number of ways to measure conversion to Parkinson’s. In one, an investigator notes slowness and one other Parkinson’s-associated symptom in a diagnostic questionnaire. With this data-driven criteria, 33 people from at-risk cohorts have developed PD (3 with a GBA mutation, 4 with smell loss, 9 with REM sleep behavior disorder, and 17 with a LRRK2 mutation).
  • The other measure is a clinical diagnosis from the investigator. Of those 33, nine were clinically diagnosed with PD and eight with motor symptoms that may be indicative of early disease. Chahine and others continue to investigate the overlap in these groups and what measure is best to assess Parkinson’s in PPMI and other studies.

New Initiatives

PPMI is following up on early findings to optimize measurement of Parkinson’s, performing deep analysis on study samples and collaborating to broaden use of its rich database. These efforts illustrate the study’s continued commitment to improvement.

• Marek reviewed a new add-on study utilizing the PPMI infrastructure to optimize brain imaging to measure disease. Fifty newly diagnosed patients will receive two different scans. The first is a DATscan, which is commercially available and has been used in PPMI since the start of the study. The second is a vesicular monoamine transporter (VMAT) scan, which is a newer technology. The purpose of the study is to see if there are advantages to one scan compared to the other. Preliminary results from PPMI suggest that VMAT may be more sensitive at detecting changes seen in PD. The study also will assess the rate of change in the dopamine signal from both scans early in disease (6, 12 and 18 months from first scan) to evaluate if these scans could help determine therapeutic impact early in clinical trials of new drugs.  
• David Craig, PhD, from the University of Southern California, outlined work from his group and partners to sequence the RNA of more than 1,600 participants in PPMI. Profiling gene expression and the impact of different factors (from age to medication use) can help better define disease progression and highlight potential measures and treatment targets. Stay tuned for more on this project when the data becomes publicly available this summer.
• Open-access data is a tenet of PPMI, and representatives from two data platforms presented at the annual meeting on efforts to make study data more accessible and useful. The study is partnering with data integration and analysis company Blackfynn to bring together the many types of data collected in PPMI (i.e., clinical, imaging, sensor) to understand and compare them for meaningful insights. Additionally, a partnership with data platform BRAIN Commons stores PPMI data alongside study data on other diseases to better understand brain health and disease.

Additional Data Collection

Since its launch, PPMI has added new ways to gather information on Parkinson’s experience and biology to continue improving the study and building toward new insights.
 

• Marek noted the move into digital health data capture with the addition of the Verily Study Watch and a Roche PD monitoring smartphone application. More than 220 participants from the United States are streaming data through the watch, and a first volunteer from the Barcelona site has started using the Roche app, which will be utilized in European PPMI sites. These digital health devices are collecting information on daily life with Parkinson’s to better measure the disease outside the clinic.
• Thomas Montine, MD, PhD, of Stanford University, shared data from the PPMI Pathology Core, which is collecting brain tissue samples from participants after death to measure pathological changes in the brain. Collection plans are in place for nearly 130 participants, and the core has collected samples from five volunteers. They are planning an expansion to European sites.

In his parting remarks, Marek commented on the evolution of the study and challenged its leaders to think bigger.

“What has been so striking is how much energy we have in the study 10 years in, how much we're talking about projects that are just beginning or emerging or maturing,” he said. “A theme we've had is how can we take advantage of the data we have and think bigger. This is a real moment and should invigorate us even further.”