An exploratory study published in Nature investigates serum neurofilament light chain (sNfL) as a potential biomarker for Fabry disease (FD). The research, conducted on a large cohort of Fabry disease patients (PwFD), reveals that sNfL concentrations are significantly higher in PwFD compared to healthy controls and correlate with disease severity.
The study found that sNfL levels were significantly higher in PwFD with ischemic white matter lesions (iWML) (p = 0.03). This finding aligns with previous research showing increased sNfL in individuals with ischemic stroke and other conditions involving white matter. According to the researchers, comparison of PwFD without iWML lesions and healthy controls was not significant (p = 0.34).
Key Findings on sNfL and Fabry Disease
The research team assessed sNfL concentrations in a large, representative cohort of PwFD and found several key correlations:
- Elevated sNfL in PwFD: sNfL concentrations were significantly higher in PwFD compared to healthy controls.
- Correlation with iWML: sNfL levels were significantly higher in PwFD with iWML, indicating a potential link between sNfL and central nervous system involvement in Fabry disease.
- Association with Disease Severity: sNfL levels correlated with clinical and paraclinical parameters of disease severity, such as the FOS-MSSI score.
Implications for Patient Monitoring
The study suggests that monitoring sNfL levels could help assess CNS integrity in Fabry disease patients, potentially reducing the need for costly annual MRIs. "This association of increased sNfL and white matter lesions might help in routine patient care to monitor CNS integrity, without requiring a costly annual MRI," the authors noted.
Influence of Disease-Specific Therapy and Renal Function
The study also explored the impact of disease-specific therapy on sNfL levels. While initial analysis showed a significant difference in sNfL absolute values between PwFD receiving therapy and treatment-naïve PwFD (p = 0.015), this significance was not maintained when analyzing Z-scores (p = 0.094). The researchers suggest that the absence of disease-specific therapy may reflect milder disease severity.
Interestingly, the study found a correlation between sNfL Z-scores and serum creatinine and eGFR, hinting at a potential link between increased blood-NfL and reduced renal function. The authors propose that impaired lysosomal metabolism in Fabry disease could contribute to rising sNfL levels over time.
Study Limitations and Future Directions
The researchers acknowledge several limitations, including the potential for small sample sizes within subgroups to interfere with statistical testing. They emphasize the need for larger samples to verify differences and extrapolations based on subgroups. Additionally, they call for longitudinal data to further evaluate the role of sNfL as a biomarker in Fabry disease.
"A single-timepoint analysis of a biomarker in FD could fall short of detecting meaningful changes over time, hence a more detailed investigation including longitudinal data is required to further evaluate the role of sNfL as a biomarker in FD," the authors conclude.
