It was important for the inclusion criteria of the tofersen studies that, in the case of genetic diseases, the 1 + 1 rule is also fulfilled if a lower neuron deficit is seen clinically at a single extremity and—in addition—the patient carries a disease-causing mutation.7,21 This criterion was the basis of early inclusion of patients carrying a SOD1 mutation into the therapeutic trial. Here, SOD1 is linked to hereditary disease.