By Clinical Research News Staff 

August 12, 2026 | Investigators at the University of Miami Miller School of Medicine reported that a 19-protein blood biomarker panel, which includes neurofilament light chain (NfL), accurately predicted the transition from presymptomatic disease to clinical amyotrophic lateral sclerosis (ALS), known as phenoconversion, across timeframes ranging from six months to five years. The findings, published in Nature Medicine (DOI: 10.1038/s41591-026-04528-x), build on nearly two decades of work through the Pre-Symptomatic Familial ALS (Pre-fALS) study. 

ALS therapeutic development efforts have repeatedly hit roadblocks, according to Michael Benatar, M.D., Ph.D., professor of neurology and public health sciences, who co-leads the study with Joanne Wuu, Sc.M. Identifying biomarkers that signal disease activity before symptoms emerge could allow therapeutic intervention during a critical presymptomatic window. 

Launched in 2007, Pre-fALS follows healthy individuals carrying genetic variants associated with inherited ALS, which accounts for roughly 10-15% of cases. Longitudinal blood samples from participants first established NfL as an early indicator of neuroaxonal injury years before symptom onset, laying the groundwork for the ongoing ATLAS clinical trial evaluating presymptomatic treatment with the SOD1-lowering antisense oligonucleotide (tofersen) in people carrying pathogenic SOD1 variants. 

While NfL has proven valuable, the latest study expands the biomarker landscape considerably. Researchers analyzed more than 500 serial plasma samples using the Olink proteomics platform, measuring approximately 5,000 proteins. They identified 92 proteins that changed before symptom onset, then used machine learning to refine the findings into a 19-protein panel that outperformed NfL alone in estimating time to phenoconversion. The results were partially replicated using data from the UK Biobank, supporting the broader relevance of the biomarker signature. 

The findings remain exploratory. Additional validation will be required before the panel can be incorporated into clinical trials or routine care. Researchers are now evaluating cerebrospinal fluid samples and additional proteomic technologies to further refine the biomarker set while developing robust clinical assays suitable for widespread use. 

If validated, the biomarker panel could provide investigators with a practical tool for identifying individuals most likely to benefit from preventive therapies, predicting future risk of phenoconversion, and moving the field closer to intervening before ALS symptoms become irreversible. 

To read the full story written by Deborah Borfitz, visit Diagnostics World News.