Objective: To validate the role of NfL for disease progression, severity and subject trial selection in MSA. Neurofilament light (NfL) was explored in this regard though in MSA findings are limited by small sample sizes.

Background: No blood test has been validated in MSA to correlate with disease severity or with prognostic value that would better inform the design of drug trials, stratification, or quantification of patient response to treatment. NfL was explored in this regard though in MSA findings are limited by small sample sizes.

Method: Cohort study recruiting cross-sectional and longitudinal MSA cases in multicentre European set-up. Plasma and cerebrospinal fluid (CSF) NfL concentrations were measured at baseline from 212 MSA cases, and annually in 44 MSA patients and 40 matched healthy controls (HC) on a Simoa HD-1 Analyzer, in conjunction with clinical, neuropsychological and MRI brain assessments. In 105 MSA cases and 36 HC we had paired plasma and CSF samples. We used Cox regression to assess survival, polynomial models to determine the trajectories of NfL in MSA disease, multivariate linear mixed effects models to analyse NfL changes longitudinally and for correlation with clinical and imaging parameters. We estimated sample sizes for trials aiming to decrease neurofilament levels.

Results: In plasma-CSF-matched samples, the correlation becomes stronger as the disease progresses, with higher fold-change in CSF compared to plasma in early disease, but  similar fold-changes and stronger correlation between CSF and plasma-derived NfL in later disease. We found a statistically significant correlation between plasma NfL levels at baseline and disease severity represented by UMSARS and disease milestones. Higher baseline plasma NfL levels were associated with more rapid clinical progression, shorter survival and higher degree of brain atrophy. Modelling of MSA progression using plasma NfL and UMSARS indicated that NfL levels rise as the motor symptoms worsen, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower participant numbers would be needed to demonstrate treatment effects when incorporating plasma NfL values into MSA clinical trials.

Conclusion: Plasma NfL is a promising biomarker for clinical disease severity, progression, and prognosis in MSA. NfL can potentially inform patient stratification and serve as reliable treatment response measure in future MSA trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/blood-nfl-can-track-progression-in-multiple-system-atrophy/