Nusinersen in spinal muscular atrophy type 1 from neonates to young adult: 1-year data from three Asia-Pacific regions.

Spinal muscular atrophy type I (SMA1) is the most common and severest form of SMA. According to natural history studies, affected babies never achieve independent sitting, and the combined median age of death or permanent ventilation is 13.5 months.1 Nusinersen, an antisense oligonucleotide that modifies survival motor neuron ( SMN2 ) splicing to enhance full-length SMN protein expression, is the first of many promising approved SMA treatments. The ENDEAR nusinersen clinical trial on SMA1 in patients aged <7 months showed promising motor milestone achievements and improved survival.2 Through this multinational study, we provide the first Asian real-world data on patients with SMA1 after 1 year of nusinersen treatment. This retrospective observational cohort study, involving eight institutes in three Asian regions (Hong Kong SAR, Taiwan and South Korea) evaluated the baseline clinical characteristics, motor outcomes and changes in ventilation needs of participating patients with SMA1, from pre-treatment (M0) to 6 months (M6) and 10 months (M10) post-treatment. All participants started nusinersen under the Expanded Access Programme (EAP) between 2017 and 2019. Baseline information — newborn screening where applicable, SMN1 mutation, SMN2 copies, gestational age at birth, sex, age of symptom onset, body weight, respiratory support, feeding status, musculoskeletal status and age of first nusinersen — was collected. The motor outcomes before and after nusinersen initiation, measured by Hammersmith Infant Neurologic Examination Part 2 motor milestones score (HINE-2), CHOP INTEND and motor milestone achievements, were recorded. We used CHOP INTEND increased ≥4 points and HINE-2 gained ≥5 points as clinical meaningful improvement.2 The study was approved by the ethics committees of individual regions. ### Statistical analysis Baseline demographics and clinical characteristics were presented using descriptive statistics. Changes in the median scores of HINE-2 and CHOP INTEND were calculated using one-way repeated measures ANOVA and paired t-test for quantitative and qualitative variables, respectively. Missing data were …