Spinal muscular atrophy (SMA) is currently classified into 5 different subtypes, from most severe (type 0) to the mildest (type 4) depending on the age of onset of the disease, the best motor function achieved and the number of copies of the SMN2 gene. Two recently approved treatments for SMA patients have revolutionized patients’ quality of life and their perspectives. However, during treatment with nusinersen, the most widely administered treatment so far, a high degree of variability in the therapeutic response has been observed in adult patients with SMA. These data, along with the lack of information on the natural history and broad spectrum of disease phenotypes, suggest that further efforts are needed to develop precision medicine approaches for all SMA patients.
Here, the authors compile current methods for the functional assessment of adult SMA patients treated with nusinersen. They also provide an overview of the known molecular changes underlying the heterogeneity of the disease. Finally, the researchers highlight the need for new techniques, i.e. -omics approaches, to capture phenotypic differences and understand the biological signature in order to revise the disease classification and personalized treatments.