On Jul. 27, 2026, an international research team led by University of Miami Miller School of Medicine scientists has identified blood-based protein signatures that predict when genetically at-risk individuals are likely to develop ALS symptoms, creating new opportunities for prevention trials and earlier intervention.

Genetic inheritance can determine a person’s health destiny. But not always. This is certainly true for people with genes that make them susceptible to amyotrophic lateral sclerosis (ALS). Some people progress from being high-risk to actually having the disease when they are relatively young. Some develop symptoms later in life. Still others never get the disease.

This has been an intractable problem for patients, clinicians and researchers. Without a way to predict if and when disease symptoms will emerge, it is difficult (if not impossible) to know who should be studied in a clinical trial or offered early therapeutic intervention.

Published in the journal Nature Medicine, these insights shed new light on the biology of pre-symptomatic ALS and could empower future prevention trials.

“By studying blood samples from people at elevated genetic risk for ALS, we identified protein signatures that predict whether someone is going to phenoconvert in the relatively near future,” said Michael Benatar, M.D., Ph.D., the Walter Bradly Chair in ALS Research, chief of the Neuromuscular Division and professor of neurology at the Miller School and executive director of the ALS Center. Dr. Benatar is senior author on the study. “This could be an incredibly valuable tool for us to select appropriate people for inclusion in future ALS prevention trials and ultimately to develop effective treatments.”

Though completed recently, the analyses in this publication were almost 20 years in the making. In 2007, Dr. Benatar, along with Joanne Wu, Sc.M., research associate professor of neurology, launched the Pre-Symptomatic Familial ALS (Pre-fALS) study. Pre-fALS tracks people with elevated genetic susceptibility to ALS, as well as ALS and frontotemporal dementia (FTD). Using a wide variety of assessment techniques (neurological exams, blood draws, cerebrospinal fluid collection and others), the study has shed light on the earliest biological changes in people destined to develop ALS and ALS-FTD.

This long view paid big dividends. Pre-fALS helped the team identify a biomarker called neurofilament light chain, a protein that enters the spinal fluid and blood when neurons are damaged. This knowledge was critical to design the ATLAS study, a pivotal phase 3 clinical trial that will help determine the optimal timing to deliver the ALS drug, Qalsody. ATLAS will also test whether Qualsody can delay or prevent ALS symptoms in unaffected people who carry a mutated SOD1 gene. Still, researchers and clinicians have needed additional biomarkers.