Biomarker Advancement Programs

Developing Biomarkers for Parkinson's Disease

The Foundation’s collective efforts seek to measure PD biology using sensitive, reliable and quantitative methods to speed clinical testing of promising PD therapies. We focus on a range of technologies including brain imaging and biofluid tests to develop additional biomarkers.

Biomarkers are essential tools for developing and testing therapies, offering a range of insights from risk detection, diagnosis, prognosis, disease monitoring, treatment response and safety assessment. The development of biomarkers is a multistep process from initial discovery through optimization and ultimate validation. Success requires access to well-characterized cohorts of people living with PD along with rigorously collected biosamples and clinical data, such as from The Michael J. Fox Foundation’s (MJFF) flagship Parkinson’s Progression Markers Initiative (PPMI). As a key part of our goal to accelerate and improve clinical trials, MJFF has been a longstanding leader in enabling the development of biomarkers for PD. 

A current focus of MJFF’s biomarker programs is to advance measures of two key pathological hallmarks of PD: accumulation of the protein alpha-synuclein and degeneration of dopamine neurons. These hallmarks are core to many of the primary movement symptoms associated with PD. In addition, while not as advanced, a range of programs are exploring measures of other PD-relevant biological pathways, such as those linked to endolysosomal, immune/inflammation and mitochondrial health. Separately, MJFF also is focused on establishing more sensitive clinical assessments for use as clinical trial endpoints. 

Success Story: Alpha-synuclein Seeding Amplification Assay 

A major advance and testament to MJFF’s efforts is the validation of a seeding amplification assay (SAA) for a key biological hallmark of PD: misfolded alpha-synuclein protein. Building off several years of work by MJFF-funded researchers along with data and biosamples from PPMI, the alpha-synuclein SAA offers for the first time an ability to detect the misfolded protein in living people, even years before symptoms begin. A powerful research tool for identifying people to participate in clinical trials, the alpha-synuclein SAA may allow for earlier testing of disease-modifying therapies and ensure people receiving treatment exhibit the biological pathology being targeted. In response to the immense value the alpha-synuclein SAA brings, MJFF has initiated a robust funding stream to support projects that expand the capabilities of this biomarker, such as by establishing methods that are more quantitative and that use less invasive biofluids or tissues. 

The Work Ahead: Biomarker Advancement Program Areas 

MJFF’s biomarker programs encompass a range of strategies and approaches. Working with field experts through coordinated consortia or traditional funding opportunities, these efforts ultimately seek to supercharge clinical trials by allowing researchers to track biological changes over time, giving them an objective measure of whether a treatment is affecting targeted biology. 

Biomarker Discovery Programs 

There remains significant room for discovering new biomarkers in Parkinson’s research, which is especially important for empowering clinical trials to more directly track biological changes linked to a treatment. Biomarker discovery efforts apply to all kinds of biological signals, ranging from tracking proteins to measuring metabolic changes. These efforts help find new and relevant markers. Detecting these markers in living people gives incredible insight into how PD functions biologically and how it might be treated. Current MJFF efforts in Biomarker Discovery include top-down generation of molecular profiling data in the Parkinson’s Progression Marker Initiative and other related cohorts. Additionally, MJFF partners with the Accelerated Medicines Partnership (AMP-PD) and the Global Neurodegeneration Proteomics Consortium to integrate harmonized molecular datasets for biomarker and target discovery.   

Targeted Pathway Programs 

While attempts to measure protein pathologies such as alpha-synuclein are important, MJFF also supports biomarker research on other biological pathways linked to PD. Many currently active therapeutic programs target PD-related neuroinflammation and lysosomal and mitochondrial dysfunction. MJFF has an active portfolio of projects seeking to develop, optimize, and validate measurements that detect and quantify changes in these disrupted biological pathways. Having sensitive measures for changes in these pathways can improve patient selection, increase understanding of drug response and help determine treatment efficacy. 

Imaging Programs 

Neuroimaging remains a highly promising tool for characterizing biology in people with PD. While MJFF continues to aggressively fund imaging tracers for alpha-synuclein pathology, the Foundation also supports the development of imaging tools that can detect and measure other indicators of PD biology, including neuroinflammation and mitochondrial dysfunction. These efforts include our MJFF Imaging Consortium, a precompetitive partnership with industry to accelerate the development and availability of novel molecular imaging radiotracers for PD. 

Quantitative Biomarker Program 

A key focus of our work is to develop quantitative measures of PD biology, which would allow researchers and clinicians to go beyond detecting whether biology is simply present and also quantify that biology from its first emergence through its development over time. Being able to objectively measure such changes may offer a more direct and informative way to determine if a therapy is having a meaningful impact on disease biology. MJFF has a robust and growing portfolio of projects seeking to improve the quantification of leading biofluid and imaging measures for future PD clinical trials.  

Available Resources: The Parkinson’s Progression Markers Initiative 

Accelerating Medicines Partnership® Parkinson's Disease database 

Parkinson’s Biomarker Pipeline Report | Zenodo 

The Michael J. Fox Foundation’s Biospecimen Resources 

If you have questions about the program or are interested in contributing, please email us at biomarkers@michaeljfox.org.