,68 Recent trial designs for disease-modifying treatments accommodate this experience by focusing exclusively on early and/or mild disease stages, e.g., the A4 study evaluating amyloid-lowering treatments in elderly individuals at risk for memory loss (NCT02008357),69 the AHEAD 3-45 study targeting preclinical AD (NCT04468659),70 or a trial testing tofersen, an intrathecally applied ASO, for pre-symptomatic SOD1 mutation carriers at risk for developing ALS (NCT04856982).71 The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.