Nigel Leigh, PhD, MBBS, PhD, FRCP, FAAN, FMedSci, University of Sussex, Brighton, UK discusses different models for researching amyotrophic lateral sclerosis (ALS). To date, animal models have not been successful in aiding ALS drug discovery. However, while biological differences limit their use in therapeutic development, animal models can provide fundamental insights into the mechanisms of neuronal damage. Prof. Leigh describes a novel approach – the experimental medicine approach – to ALS clinical trials. This approach encompasses studies of numerous markers that shed light on a patient’s response to treatment in a given trial, including liquid biomarkers and gene expression profiles. Overall, this approach is costly but may help to limit trial failure in the future. This interview was conducted during the 2022 World Congress on Controversies in Neurology (CONy) meeting.