The U.S. Food and Drug Administration (FDA) encouraged scientists and drug developers to use the alpha-synuclein seed amplification assay (αSyn-SAA) biomarker, discovered in 2023, for research and clinical trials. The FDA issued a “Letter of Support” in late Summer 2024, following multi-stakeholder collaboration amongst The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and the Critical Path Institute (C-Path), with both organizations supporting use of the biomarker for clinical trials and advancing new drugs for Parkinson’s disease (PD).
Because the tool can objectively detect early biology related to Parkinson’s and related diseases, including Dementia with Lewy Bodies (DLB), even before any symptoms emerge, trials using the biomarker are better positioned to identify participants with relevant biology and test therapies that aim to delay or even prevent the onset of disease. The use of the tool also enables research toward tailored therapies to treat individuals at all stages of these diseases.
In the letter, the FDA emphasizes that their support stems from significant evidence collected as part of MJFF’s flagship Parkinson’s Progression Markers Initiative (PPMI), which first validated the αSyn-SAA biomarker in April 2023.
This is only the second Letter of Support issued for PD markers. The first came in March 2015, when the agency issued a letter encouraging use of DaTScan to image dopaminergic transport dysfunction.
The letter from the FDA also acknowledges the potential of a staging system for Parkinson’s and related diseases, specifically the first biological staging system known as the neuronal synuclein disease integrated staging system (NSD-ISS). Early in 2024, a multistakeholder team including academic researchers and clinician scientists, industry, nonprofits, regulators, and people affected by Parkinson’s worked together to develop the staging system. NSD-ISS was made possible by the newfound ability to detect misfolded alpha-synuclein. The FDA Letter of Support recognizes the potential of NSD-ISS, alongside data generated by αSyn-SAA to accelerate the success of scientific discovery and therapeutic development.
“This FDA Letter of Support is a transformative moment for the field, promising to speed clinical trial design in Parkinson’s and related disorders,” said Diane Stephenson, PhD, executive director, CPP, C-Path. “The cross-collaboration among patients, researchers, clinicians, regulators and patient advocacy organizations demonstrates the critical role every player holds in moving today’s achievement forward. Now, we’re closer than ever to better treatments, and perhaps one day, preventing people from developing the symptoms of these diseases altogether.”
The FDA’s Letter of Support notes that important data supporting αSyn-SAA emerged from the Foundation’s landmark PPMI study, with more than a dozen other major international longitudinal studies corroborating. PPMI has built the most robust dataset and biosample library ever assembled in Parkinson’s research, which is shared with the broader research community in real time for ongoing discovery and validation studies. Heralded as “the study that’s changing everything” about how Parkinson’s is diagnosed, managed and treated, PPMI and its data are made possible by more than 3,000 in-clinic and 42,000 online research volunteers with and without Parkinson’s disease. The Letter of Support states: “Key success factors for PPMI include the alignment, harmonization, and transparency of data collection methodologies and open sharing of data.”
“The search for a Parkinson’s biomarker has been a centerpiece of The Michael J. Fox Foundation’s mission-critical work since our earliest days,” said Todd Sherer, PhD, MJFF’s chief mission officer. “As we continue working urgently toward better treatments and a cure, the FDA’s backing of αSyn-SAA is an important milestone in advancing today’s robust pipeline of Parkinson’s therapies that patients and families urgently need.”
Clinical trials for potential new Parkinson’s therapies are historically time-consuming and costly. From testing through approval, the development of a single new therapy takes decades and costs billions of dollars. As an objective and reliable biomarker of Parkinson’s biology supported by the FDA, αSyn-SAA holds potential to make these trials faster, clearer and more efficient, significantly decreasing the risk for industry to invest in the development of potential blockbuster therapies, including preventive agents. With αSyn-SAA in hand, it will be possible to establish objective endpoints for clinical trials of Parkinson’s treatments, ensure study participants exhibit relevant pathology, and detect therapy-induced changes in their status.
“In my conversations to my fellow patients, I have used the analogy of previous Parkinson's drug research as ‘cave exploration in the dark’,” said Kevin Kwok, PharmD, former biopharmaceutical executive, PPMI community advisory board member and patient advocate diagnosed with PD in 2009. “PPMI's biomarker initiative has resulted in the creation of an alpha-synuclein ‘lantern’ so we are no longer groping in the darkness but now have biological illumination of the cavern we are exploring.”