BLOOD neurofilament light emerged as a promising biomarker for measuring treatment response in neurodegenerative disease trials, offering a potential innovation that could streamline future drug development and improve evaluation of emerging therapies.
Developing effective treatments for neurodegenerative diseases remains challenging, partly because demonstrating meaningful clinical benefit often requires lengthy and complex studies. Researchers are increasingly exploring blood based biomarkers that could provide earlier and more objective measures of treatment response. A new scoping review suggests that blood neurofilament light may offer one such opportunity, with growing evidence supporting its use as a surrogate endpoint in clinical trials.
The review examined studies published between 2013 and 2024 that evaluated serum or plasma neurofilament light as an endpoint in interventional clinical trials. In total, 49 studies were included, comprising 29 in multiple sclerosis, eight in amyotrophic lateral sclerosis, six in Alzheimer’s disease, and six involving other neurodegenerative conditions.
Across many studies, reductions in blood neurofilament light were accompanied by improvements in primary efficacy outcomes, supporting its role as a marker of neuroaxonal injury, disease activity, and treatment response. The findings suggest that blood sampling could provide investigators with a less invasive method of monitoring biological changes during clinical trials compared with cerebrospinal fluid analysis.
However, the review also identified important limitations. Several studies found that changes in blood neurofilament light did not correspond with clinical outcomes, particularly where interventions were not designed to modify the underlying disease process. These findings indicate that interpretation of biomarker results must take both disease biology and treatment mechanism into account.
The authors concluded that blood neurofilament light has considerable potential to modernise neurological clinical trials by serving as a surrogate endpoint, particularly in disorders characterised by active neuroaxonal injury. If validated further, the biomarker could help researchers evaluate treatment effects more efficiently and potentially accelerate the development of new therapies.
At the same time, the review emphasises that widespread adoption will require disease specific validation and a clearer understanding of how blood neurofilament light behaves across different therapeutic approaches. Rather than replacing conventional clinical outcome measures, the biomarker is likely to complement them by providing objective biological evidence of treatment response.
As precision medicine continues to reshape neurology, blood based biomarkers such as neurofilament light may represent an important step towards more efficient, less invasive, and biologically informed clinical trial design.
Zheng Y et al. Use of blood-based neurofilament light chain as an endpoint in clinical trials of neurodegenerative conditions: a scoping review. J Neurol. 2026;273(8):476.
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