Project Grant R01AG103000

The National Institute on Aging awarded the University of Miami $3.73 million on September 1, 2026, under the Aging Research program (CFDA 93.866) to develop and internally validate predictive markers and a composite risk score for phenoconversion to clinically manifest amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) in C9ORF72 repeat expansion carriers. The award funds evaluation of leading clinical markers and biomarkers—including presence of prodromal syndrome, thalamic volume, plasma NFL concentration, C9ORF72 repeat length, and personalized penetrance estimates—for their utility in predicting time to phenoconversion, a likely primary endpoint in future prevention trials. The recipient, University of Miami's Office of Research Administration—School of Medicine Division in Miami, Florida, will conduct the work through August 31, 2031. The project addresses a critical gap in C9ORF72 prevention trial readiness: unlike familial Alzheimer's disease or Huntington's disease, no reliable individual-level predictors of onset age have been identified among C9ORF72 carriers, though they typically develop clinically manifest disease in their 50s and 60s. The work hypothesizes that predictive utility will increase when these markers are considered together, enabling identification of expansion carriers at greatest short-term risk for therapeutic intervention while still pre-symptomatic.