Abstract:Background:The introduction of spinal muscular dystrophy (SMA) modifying therapies, such as antisense oligonucleotide therapy has changed the natural history of SMA. Most reports on treatment outcomes have focused on motor scores and respiratory function. However, the impact of this novel therapy on the progression of scoliosis is not known. The objective of this study is to document the development and progression of scoliosis in patients with SMA1 treated with nusinersen.Methods:A descriptive single center study was conducted with patients with SMA1 who were treated with nusinersen before 6 months of age. Data was collected on patients who met criteria, including age at the first nusinersen dose, number of nusinersen doses, degree of scoliosis, respiratory parameters, feeding route and motor scores at baseline and follow-up. CHOP-INTEND was sub-analyzed using axial (AxS) and appendicular motor scores (ApS) to evaluate a possible correlation between scoliosis and axial muscle strength.Results:From our cohort, thirty-one percent (11/35) of patients had a diagnosis of SMA1. Sixty-three percent (7/11) met the inclusion criteria. All patients (7/7) showed initial improvement in their CHOP-INTEND scores in correlation with improvement on the ApS. Despite this, the majority of patients did not show no improvement in the AxS. Subsequently, all patients developed scoliosis in the first year of life with Cobb angles that ranged between 18-60 degrees. Furthermore, total CHOP-INTEND scores had dropped in two patients alongside the development of a Cobb angle of > 40 degrees.Conclusion:Despite the significant improvement in functional motor assessment in patients with SMA1, there is progression of significant scoliosis despite treatment. Subsequently, lack or minimal improvement on the axial CHOP-INTEND scores may predict worsening on the total motor scores.

ObjectiveSpinal muscular atrophy (SMA) is a neuromuscular disorder that manifests with motor deterioration and respiratory complications. The paradigm of care is shifting as disease-modifying therapies including nusinersen, onasemnogene abeparvovec and risdiplam alter the disease trajectory of SMA. The objective of this study was to explore caregivers’ experiences with disease-modifying therapies for SMA.DesignQualitative study including semistructured interviews with caregivers of children with SMA who received disease-modifying therapies. Interviews were audio recorded, transcribed verbatim, coded and analysed using content analysis.SettingThe Hospital for Sick Children (Toronto, Canada).ResultsFifteen family caregivers of children with SMA type 1 (n=5), type 2 (n=5) and type 3 (n=5) participated. There were two emerging themes and several subthemes (in parentheses): (1) inequities in access to disease-modifying therapies (variable regulatory approvals, prohibitively expensive therapies and insufficient infrastructure) and (2) patient and family experience with disease-modifying therapies (decision making, hope, fear and uncertainty).ConclusionThe caregiver experience with SMA has been transformed by the advent of disease-modifying therapies. Consistent and predictable access to disease-modifying therapies is a major concern for caregivers of children with SMA but is influenced by regulatory approvals, funding and eligibility criteria that are heterogenous across jurisdictions. Many caregivers described going to great lengths to access therapies, highlighting issues related to justice, such as equity and access. This diverse population reflects contemporary patients and families with SMA; their broad experiences may inform the healthcare delivery of other emerging orphan drugs.

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