Using Nusinersen in Type 0 SMA Led to Mild Benefits, Case Study Shows

A case report of a male infant with type 0 spinal muscular atrophy (SMA) is offering evidence of the use of nusinersen in this setting.

Following treatment with nusinersen, the researchers observed mild improvements, which they noted is not typically seen in type 0 SMA and confirms the treatment’s relative efficacy in the most severely affected infants.

More severe than type 1 SMA, type 0 SMA is “characterized by a clear prenatal history of reduced fetal movements and is associated, at birth, with profound hypotonia and weakness, contractures, feeding difficulties, and severe respiratory insufficiency with need for resuscitation and mechanical ventilation support,” explained the researchers.

The infant began treatment with nusinersen at age 13 days, with mild improvements observed approximately 2 months after the initiation of treatment. Improvements included small distal movements and improvement in respiratory drive, with some attempts of spontaneous breathing while on invasive ventilatory support.

At the time of treatment, there was just 1 paper documenting the use of nusinersen in a case of more mild type 0 SMA. The researchers noted that the choice to initiate nusinersen for their infant was very controversial and required involvement of their ethics board. They explained: “The lack of published data left room for hope for not only the families but also for our ethic board who felt that a possible improvement with prolonged survival could not be excluded a priori.”

Prior to starting treatment, the infant had very poor respiratory drive and was on invasive respiratory support full time. According to the researchers, there was an attempt to reduce the level of ventilation through a trial of continuous positive airway pressure (CPAP) of of 6 cmH2O by endotracheal tube (ETT), although it failed within 5 minutes of the trial when the infant experienced severe hypoxia, requiring immediate mechanical ventilation.

Following treatment with nusinersen, the researchers performed a second attempt of an ETT CPAP trial. Respiratory function was improved compared with the first trial, and the infant was able to tolerate the trial significantly longer, for 55 until the infant experienced severe bradycardia, hyperglycemia, profuse sweating, and systemic hypertension.

“Our findings suggest that despite treatment may have produced some minimal improvement on mobility and, to some extent on respiratory function, the effect was not enough to contrast the overall severity and the multisystemic involvement,” wrote the researchers, noting that bradycardia seemed to be the most limiting factor in considering noninvasive intervention.

At 3 months, the infant’s parents opted for tracheostomy and gastrostomy, which resulted in a further increase in distal improvements in upper and lower limbs. However, despite the interventional approach, the infant’s cardiac function deteriorated, leading to cardiac arrest at 5 months.

Reference

Tiberi E, Coasta S, Pane M, et al. Nusinersen in type 0 spinal muscular atrophy: should we treat? Ann Clin Transl Neurol. Published online November 4, 2020. doi: 10.1002/acn3.51126.