In this issue, Dr Gauvreau et al. present their experience with nusinersen treatment in spinal muscular atrophy (SMA) type 1, focusing on its long-term effects on respiratory and bulbar function. Their study provides valuable real-world data on a patient population already exhibiting clear clinical symptoms at treatment initiation.

While nusinersen significantly improves survival and motor function in SMA type 1,^{Reference Finkel, Mercuri and Darras1} its impact on respiratory outcomes remains less clear.^{Reference Lagae, Proesmans, Van den Hauwe, Vermeulen, De Waele and Boon2} The study’s findings are somewhat disappointing, as many patients continue to require ventilatory and nutritional support despite treatment. Notably, age at treatment initiation (≤ or >2 years) did not appear to influence the trajectory of respiratory and bulbar function, suggesting that time since symptom onset and disease severity at treatment initiation may be more critical factors. Given the irreversible motor neuron loss, nusinersen may primarily stabilize rather than improve clinical function in symptomatic patients.

Bulbar dysfunction, regardless of treatment timing, remains a major challenge. One possible explanation is the suboptimal rostral penetration of nusinersen after intrathecal administration. Persistent bulbar symptoms can exacerbate respiratory symptoms through increased aspiration risk, reduced cough efficiency and sustained progressive chronic respiratory infections. These findings highlight the unmet need for treatment strategies that better target the bulbar region to prevent long-term respiratory decline.

The study reinforces the importance of early, presymptomatic diagnosis and intervention in SMA. All newborns and their families deserve access to newborn screening, coupled with early genetic confirmation to guide treatment decisions. Despite strong evidence supporting its necessity, only 31 countries^{Reference Vrščaj, Dangouloff, Osredkar and Servais3} have implemented newborn screening for SMA, highlighting a global disparity in access to early diagnosis and treatment. Addressing this gap is crucial for ensuring equitable care for affected patients.

In conclusion, while nusinersen has transformed the SMA treatment landscape, its limitations in symptomatic patients are evident. This study adds to the growing evidence that treatment initiation after symptom onset is often insufficient to prevent significant neuromotor and respiratory disabilities in SMA type 1 – raising concerns of “too little, too late.” Parents should receive thorough counseling before treatment initiation, as survival will improve, but often with considerable disability and reduced quality of life. These findings highlight the urgent need for newborn screening and presymptomatic treatment as the global standard of care. Future research must focus on optimizing treatment strategies, particularly improving drug delivery to the rostral region that controls bulbar function, to enhance outcomes for SMA patients.