Unravelling dynamic trajectories of epistemic emotions in a technology-enhanced problem-solving task: A multimodal data approach.

Spinal Muscular Atrophy (SMA) is a rare neuromuscular disease that causes progressive weakness in the limbs and trunk and atrophy of the muscles. The hallmark of the disease is the degeneration of anterior horn cells in the spinal cord, giving rise to the characteristic muscle atrophy of varying degrees. The most common form of SMA which accounts for over 95% of cases is the autosomal recessive form that results from a homozygous deletion in the survival of motor neuron 1 (SMN1) gene – also known as 5q SMA. This form of SMA is one of the most common genetic causes of childhood mortality, however the phenotype of the disease is largely variable and is classified into five main types (type 0 to 4) based on age of onset and achieved motor milestones. An almost identical copy of the SMN1 gene, SMN2 also contributes to the phenotypic classification, with the clinical severity inversely correlating with the SMN2 gene copy number. Although a monogenetic disease, SMA is generally perceived as a complex disease due to the highly variable phenotypic spectrum and multiple system involvement and as such it requires a multidisciplinary care approach to be successfully managed. In addition to neuromuscular specialists, patients require a combination of respiratory, nutritional, and orthopaedic care alongside mental health support to aid in the decline of psychosocial wellbeing that is sometimes experienced by adults contemplating the progression of their disease. As new treatment options become available, the size of the adult SMA population will continuously grow, therefore establishing a standardised and structured approach to the management of adults is essential. In recent years, the treatment landscape in the SMA setting has rapidly evolved with 3 disease modifying therapies (DMT's) now available. Onasemnogene abeparvovec (Zolgensma) is the first and only approved gene therapy in SMA but is not available for older children or adults. In 2019, The National Institute for Health and Care Excellence (NICE) communicated the conditional approval of Nusinersen followed by the conditional approval of Risdiplam in 2022 under a Managed Access Agreement (MAA) in England, Wales and Northern Ireland. The commencement of an MAA allows for time limited access to new therapies that have shown promise but lack sufficient evidence to be made routinely available on the NHS whilst further evidence is compiled. The label also included treatment for adult patients however consensus on the management of SMA, particularly the development of standards of care (SoC), has focused primarily on the paediatric population with evidence suggesting a lack of co-ordination in the provision of such care in adults. In light of the rapidly developing therapy landscape, it was evident that there was an urgent need to establish stronger clinical networks and real-world data (RWD) collection to monitor and gain a better understanding of the impact of novel treatments on the natural history of the disease, particularly in the adult population where expectations of treatments were largely unknown due to lack of available data.