A state-of-the-art review of registries in spinal muscular atrophy: A valuable resource for clinical research

Since 2016/17, three disease modifying therapies for spinal muscular atrophy (SMA) have been translated into clinical practice. This has driven the implementation of newborn screening to transform health outcomes and clinical practice. SMA registries have provided important sources of data on the evolution of novel phenotypes within the therapeutic era, treatment patterns, epidemiology, genotype-phenotype correlations, care and lived experiences of people living with SMA, to enrich knowledge and learnings of the condition in this changed landscape. In this state-of-the-art review, we consider the utility and outcomes of SMA registries and evaluate their role and importance. In 2024 there are more than 35 national registries cataloguing over 8000 individuals with SMA. Additional registries are operated by advocacy groups and pharmaceutical companies, compiling data for more than 10,000 individuals with this condition. This review highlights the essential role of registries in supporting clinical trial recruitment, defining the changing incidence and prevalence of SMA in an age of reproductive carrier and newborn screening, establishing natural history data, contributing to post market drug surveillance, assessing real world clinical and cost effectiveness and capturing patient-reported outcome measures (PROMS) and experience measures (PREMS). Whilst their utility is broad, barriers to effective data curation and management are evaluated including challenges of data curation and fragmentation, quality and sharing, alongside resource constraints and sustainability. Strategies to enhance the value of registries include the imperative to collaborate across clinical research networks and the value of interoperability, enabled by standardization of data collection and entry, sharing procedures and public and patient involvement. As new phenotypes and unmet needs emerge in the post therapeutic era, registries remain central tools in generating new insights now and into the future and are poised to respond meaningfully to the priorities of individuals living with SMA.