A large, real-world study of serum NfL from people with ALS enrolled in the ARC Study

Topic:

Translational Research

Poster Number: O299

Author(s):

Fernando Vieira, MD, ALS Therapy Development Institute, Alan Premasiri, MS, ALS Therapy Development Institute, Josh Berman, ALS Therapy Development Institute, Erin Geraghty, MSN, ALS Therapy Development Institute, Joseph Gill, ALS Therapy Development Institute, Alan Gill, PhD, ALS Therapy Development Institute

Background
Neurofilament Light (NfL) is a biomarker released into blood and cerebrospinal fluid during neurodegeneration. In amyotrophic lateral sclerosis (ALS), elevated NfL levels have been associated with disease progression and therapeutic response. Recent advancements, such as the FDA-approved drug tofersen, have highlighted the clinical significance of NfL. However, its behavior in diverse ALS populations remains underexplored.

Objective
This study aimed to characterize serum NfL levels in a real-world cohort of ALS patients, leveraging 600 blood samples from 234 participants enrolled in the ALS Research Collaborative (ARC) Study.

Results
Serum NfL levels were significantly elevated in ALS patients compared to healthy controls and asymptomatic mutation carriers. Higher NfL levels correlated with faster disease progression, greater symptom severity (as measured by ALSFRS-R scores), and bulbar onset. Assay variability was observed between the LabCorp and SIMOA platforms; however, relative patterns across samples were consistent. NfL levels appeared stable across the cohort but showed variability in individuals experiencing clinical changes.

Conclusions
Serum NfL is a promising prognostic biomarker and therapeutic endpoint for ALS. However, its variability in individual trajectories underscores the need for further characterization. Future research will refine best practices for NfL measurement, evaluate outlier cases, and integrate NfL data with digital clinical outcomes to enhance its clinical utility.