# Serum neurofilament light protein as a biomarker in Niemann-Pick disease, type C1

## TL;DR

This study explores serum neurofilament light protein as a potential biomarker for monitoring and treating Niemann-Pick disease, type C1.

## Contribution

The study identifies serum NfL as a novel biomarker for NPC1, showing its correlation with disease severity and treatment response.

## Key findings

- Serum NfL levels are 6.1-fold higher in NPC1 patients compared to controls.
- NfL levels correlate with neurological severity scores and age of symptom onset.
- Miglustat treatment is associated with a 26% reduction in serum NfL levels.

## Abstract

Niemann-Pick disease, type C1 (NPC1) is a fatal, neurodegenerative disease caused by pathological variants in NPC1. Analysis of serum neurofilament light (NfL), a marker of neuronal damage, could be useful as a biomarker for patient monitoring and clinical trial design.

We measured NfL levels in serum samples from 118 well-characterized individuals with NPC1 and analyzed them with respect to clinical measures and treatment status.

The results show a 6.1-fold increase in serum NfL in individuals with NPC1 compared with age-appropriate controls. Moreover, serum NfL levels showed a significant positive correlation with age of neurological symptom onset and the annual severity increment score. Serum NfL levels were also positively correlated with the 17- and 5-domain NPC Neurological Severity Scores. Longitudinal analyses reveal a 26% reduction in serum NfL levels in individuals on miglustat, a therapeutic drug used off-label for the treatment of NPC1 in the United States of America. Effectiveness of intrathecal hydroxypropyl-β-cyclodextrin treatment may be more beneficial in younger individuals. To help inform clinical trial design, our modeling predicts that a measurable reduction of serum NfL levels might be observed after 8 months of treatment with a potential drug exhibiting 10% to 20% efficacy.

Our data suggest that NfL may be a useful serum biomarker for NPC1.