Experience of nusinersen treatment in advanced spinal muscular atrophy type 1: Characteristics of late responders with delayed treatment efficacy

Objective

Little clinical data is available for advanced cases of spinal muscular atrophy (SMA) type 1, particularly those requiring ventilation support. Therefore, this study aimed to evaluate the effectiveness of nusinersen treatment on motor and respiratory function in advanced cases of SMA type 1.

Methods

This observational cohort study included seven patients with advanced SMA type 1, requiring permanent ventilator support and tracheostomy, at Hyogo Medical University School of Medicine Hospital between July 2017 and July 2019. The primary outcome was change in motor function, assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score. Subjective changes, which could not be measured with CHOP-INTEND, were also evaluated. The secondary outcomes included changes in respiratory function, measured by tidal volume (TV) and transcutaneous carbon dioxide (TcCO₂) levels.

Results

Two patients showed a meaningful improvement in CHOP-INTEND scores (an increase of 4 points) after 2–3 years of nusinersen treatment. The remaining five showed changes ranging from 0 to 2 points. Subjective changes were observed in all patients. Patient respiratory function outcomes varied; TV increased in two patients and decreased in five, and TcCO₂ levels decreased in three patients and increased in four.

Conclusions

Nusinersen may provide meaningful improvement in motor function in some patients with advanced SMA type 1; however, treatment response may take a while and varies between individuals. Further research is needed to substantiate these findings and identify potential prognostic factors for nusinersen treatment.