INTRODUCTION/AIMS: There are currently three medications approved for spinal 
muscular atrophy (SMA), but the use of these medications in combination has not 
been well described.
METHODS: This is a retrospective report of four cases of SMA treated with dual 
onasemnogene and risdiplam therapy at our institution.
RESULTS: Following onasemnogene therapy, all four patients experienced a 
perceived plateau of therapeutic benefit, at which time daily risdiplam was 
started. Transient fatigue and weakness was seen in two patients following 
risdiplam initiation, but this resolved within 1 mo. One patient was 
hospitalized with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 
and post-viral pneumonia, weeks following risdiplam initiation. No other adverse 
effects related to onasemnogene and risdiplam combination therapy were 
identified and all patients experienced objective and subjective improvement.
DISCUSSION: Combination therapy with onasemnogene and risdiplam in patients with 
SMA appears to be well-tolerated. Further large prospective trials are needed to 
determine whether dual therapy is more efficacious than monotherapy, and to 
identify rare adverse events that may occur with the use of combination therapy.