The FDA has issued a letter of support for the use of the α-synuclein seed amplification assay (αSyn-SAA) biomarker in clinical trials for Parkinson's disease (PD) and related synucleinopathies. This endorsement aims to enhance the efficiency and accuracy of trials focused on delaying or preventing the onset of these neurodegenerative conditions. The decision follows collaborative efforts between The Michael J. Fox Foundation for Parkinson's Research (MJFF) and the Critical Path Institute (C-Path).
αSyn-SAA: A Transformative Tool
The αSyn-SAA is designed to detect early biological changes associated with Parkinson's disease, even before the emergence of clinical symptoms. This capability allows for the development of therapies tailored to individuals at all stages of the disease. The assay identifies abnormal clumps of misfolded alpha-synuclein in cerebrospinal fluid (CSF), a key pathological feature of Parkinson's and related disorders.
Todd Sherer, PhD, MJFF's chief mission officer, stated, "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. 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."
Validation and Accuracy
The FDA's support is grounded in substantial evidence, particularly data from MJFF's Parkinson's Progression Markers Initiative (PPMI). A study published in The Lancet Neurology demonstrated the high diagnostic accuracy of αSyn-SAA in identifying PD, distinguishing molecular subtypes, and detecting the disease prior to the manifestation of primary symptoms. The study, involving 1123 participants, showed a sensitivity of 88% and a specificity of 96% in differentiating PD from controls.
Clinical Implications
The use of αSyn-SAA can significantly streamline clinical trials by providing objective endpoints, ensuring that study participants exhibit relevant pathology, and facilitating the detection of therapy-induced changes. This increased efficiency can reduce the financial risks associated with developing new therapies, including preventive agents.
Diane Stephenson, PhD, executive director of the Critical Path for Parkinson's Consortium at C-Path, noted, "This FDA Letter of Support is a transformative moment for the field, promising to speed clinical trial design in Parkinson's and related disorders. 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."
NSD-ISS: A Staging System for Parkinson's
In January 2024, a team of experts introduced the neuronal alpha-synuclein disease integrated staging system (NSD-ISS), published in The Lancet Neurology. This system utilizes the αSyn-SAA-detected biomarker to identify the progression of NSD through various stages. The FDA's letter acknowledges the potential of NSD-ISS, combined with αSyn-SAA data, to accelerate therapeutic development in Parkinson's disease.
Amprion's Role
Amprion's SAAmplify-αSYN Biomarker Test is currently the only validated synSAA assay available in the U.S. to improve the diagnosis of Parkinson’s and other synucleinopathies. Russell Lebovitz, MD, PhD, Amprion’s CEO and co-founder, stated, "We are very pleased with the timing of this FDA support letter given that there are a growing number of disease-modifying drug candidates in clinical development."
