Revolutionizing Multiple System Atrophy Diagnosis With Amprion’s Synuclein Seed Amplification Assay: Russell Lebovitz, MD, PhD

WATCH TIME: 8 minutes

"MSA is not as benign a disease [as Parkinson disease], and it doesn't respond to the same treatments... it is essential to diagnose early."

Amprion’s SAAmplify-aSYN Biomarker Test is a first-in-class qualitative laboratory developed test and the only seed amplification assay available to aid the diagnosis of synucleinopathies such as Parkinson disease (PD), Lewy body dementia (LBD), and Alzheimer disease (AD) with Lewy body variant. Formerly known as SYNTap, the assay was recently studied in a multicenter cohort to determine whether it could reliably distinguish seeds from Lewy bodies and glial cytoplasmic inclusions.

Published in the Lancet Neurology, the assay was used to analyze masked cerebrospinal fluid (CSF) and brain samples from participants with multiple system atrophy (MSA), PD, DLB, isolated REM sleep behavior disorder (iRBD), non-synucleinopathy disorders, or healthy controls. In 23 brain samples from the NYBB cohort, those with Lewy bodies tested positive for synSAA and showed high fluorescence (type 1 MSA), those with glial cytoplasmic inclusions also tested positive but showed intermediate fluorescence (type 2 MSA), and samples without α-synuclein pathology showed very low fluorescence and were synSAA-negative.

In the DeNoPa research cohort, which had no samples from patients with MSA, the novel seed assay had sensitivities of 95% (95% CI, 88-99) for 80 participants with PD and 95% (95% CI, 76-100) for 21 participants with iRBD, and a specificity of 95% (95% CI, 86-99) for 60 healthy controls. When combining all the included cohorts, the novel synSAA had 87% sensitivity for MSA (95% CI, 80-93) and specific for type 2 seeds was 77% (67-85). Overall, these findings suggested that the assay produced amplification patterns that enabled the identification of underlying alpha-synuclein pathology, showing that 2 levels of fluorescence corresponded with different pathological hallmarks of synucleinopathy.

In an interview with NeurologyLive®, Russell Lebovitz, MD, PhD, discussed the mechanism and promise behind the assay, and how it could potentially revolutionize the diagnosis of MSA, which remains a challenge for clinicians. He spoke on how the assay amplifies misfolded proteins, enabling highly sensitive detection–even at concentrations as low as a few molecules. Lebovitz, chief executive officer and cofounder of Amprion, provided comment on the studies that validated the tool, as well as the importance of being able to distinguish MSA from PD and other tauopathies early on.

REFERENCE
1. Ma Y, Farris CM, Weber S, et al. Sensitivity and specificity of a seed amplification assay for diagnosis of multiple system atrophy: a multicenter cohort study. Lancet Neurol. 2024;23(12):1225-1237. doi:10.1016/S1474-4422(24)00395-8