The Michael J. Fox Foundation (MJFF) issued dozens of grants over June and July of 2025, including a concerted effort to advance a key prong of MJFF’s strategy – figuring out how to measure the misfolded proteins that are implicated in Parkinson’s progression.
This work to develop quantifying seeding amplification assays saw five new projects funded, totaling more than $4 million in research dollars.
What Do Seed Amplification Assays Tell Us?
In 2023, the research community validated a biomarker for Parkinson’s using data from The Michael J. Fox Foundation’s flagship Parkinson’s Progression Markers Initiative (PPMI).
A biomarker is a biological signature of a disease; a biomarker test, or assay, allows us to detect if the disease biology is present. For example, cholesterol can be used as a biomarker for heart disease. The biology we associate most closely with Parkinson’s disease is the misfolding of a protein called alpha-synuclein. The alpha-synuclein seeding amplification assay (SAA) tells us when the misfolded version is present. That’s a huge deal, because it enables the detection of the hallmark biology of PD in the living brain – something that was not possible before the biomarker was validated.
The Move Toward Measurement
In the spring of 2025, we launched an open call for research projects looking for ways to make the alpha-synuclein seeding amplification assay quantitative, or measurable. “The assay would not just tell us whether misfolded alpha-synuclein was present,” explains MJFF chief scientist Mark Frasier, PhD. “It would also tell us how much misfolded alpha-synuclein is present.”
Over June and July, MJFF committed grants to Brigham and Women’s Hospital, Roche Diagnostics, Prosperodes, Newcastle University and Technical University of Denmark. Each project focuses on making SAA quantitative and developing techniques for using it.
- Brigham and Women’s Hospital – Developing a highly sensitive version of the assay that works in blood, where alpha-synuclein concentrations are low. (The test is currently only validated in spinal fluid).
- Roche Diagnostics - Adapting digital assay technologies to improve the SAA test, allowing for more accurate ways to estimate the concentration of alpha-synuclein.
- Prosperodes – Testing a technology platform called SeRAS® (Seed Replication, Analysis and Subtyping) that allows precise control of the physical seed amplification reaction. This study proposes using this technology to quantify synuclein seeds.
- Newcastle University – Seeks to replace different components of SAA with modified alpha-synuclein and a new dye that can bind to and measure misfolded alpha-synuclein.
- Technical University of Denmark – Aims to make measurement via spinal fluid more sensitive for quantification, while also exploring a new type of SAA for less invasive sampling through skin and saliva.
How Measuring Helps Parkinson’s Research
Why is it a priority to measure the amount of misfolded alpha-synuclein, not just presence?
“For one,” Dr. Frasier continues, “It gives a direct window into how misfolded alpha-synuclein might change over time in Parkinson’s disease.”
This helps us understand the disease better, and in turn, can inform efforts to develop therapies. For example, some therapies seek to halt the misfolding of alpha-synuclein, others seek to reverse it. We want to be able to measure how much alpha-synuclein exists before and after testing the therapies to see how they work.
Scientists currently do not know whether misfolded alpha-synuclein matches the progression of Parkinson's symptoms, or if the amount of alpha-synuclein increases at the same rate in everyone with the disease. It is likely that some people will benefit more from synuclein-focused therapies while others may benefit from treatments that target other biology underpinning the disease. Quantitative SAA could help guide these treatment decisions.
“As we better understand Parkinson’s biology,” notes Dr. Frasier, “We can also better subdivide the disease into different types and stages, which might be treated differently.”
Additionally, quantifying SAA would be an important tool for clinical trials. For one, it would help select volunteers with similar biology, leading to more consistent results with fewer subjects. Additionally, the impact of synuclein-based therapies (or other therapies that could impact synuclein) on SAA could be monitored, as we aim to develop treatments that slow or stop the progression of Parkinson’s by reducing the amount of misfolded alpha-synuclein in the brain.
The Big Picture
The Michael J. Fox Foundation funds a huge variety of work in Parkinson’s disease, with multiple strategic initiatives getting support in June and July.
Other grants awarded include:
- The Targets to Therapies initiative funded a new project to reveal details of an underexplored target in Parkinson’s research
- Numerous grants went out the door supporting MJFF’s Therapeutic Pipeline Program, which aims to facilitate the development of new treatments for Parkinson’s.
- Significant funding continues to flow to flagship efforts like the Parkinson’s Progression Markers Initiative and the Global Parkinson’s Genetics Program, both supported by Aligning Science Across Parkinson’s (ASAP) with implementation by The Michael J. Fox Foundation. Together, these projects represent major outlays in support of Parkinson’s research, constituting $62 million in support.
Efforts to quantify the alpha-synuclein seeding amplification assay are just one facet of the overall research strategy. But that facet got a big boost over the summer of 2025.