Spinal muscular atrophy (SMA) is an autosomal recessive disease leading to progressive
muscle weakness and atrophy, in severe cases also affecting the bulbar and respiratory
muscles.The clinical spectrum of the disease is extremely variable, in the most severe
cases resulting in perinatal death, while at the least severe end of the spectrum
causing some motor deficits in old age without the loss of ambulation. Spinal muscular
atrophy care has changed dramatically in recent years due to the availability of new
therapeutic options. The FDA approved nusinersen in 2016, this was followed by the
approval of onasemnogene abeparvovec in 2019 and risdiplam in 2020. The EMA approved
all three therapies a year later. Two of the threapies work at the pre-mRNA level,
one at the DNA level. The clinical studies leading to the approval of the three drugs
included patients of different ages and clinical conditions, and utilised partly different
motor and functional scales. Therefore, direct comparison of these clinical studies
is not possible. However, an increasing amount of real-world data contribute to the
better understanding of the efficacy of the different therapies for patients of different
ages and clinical conditions, in a real-world setting. Thus, the question may arise
“Which is the best SMA therapy?”. This is an impossible question to answer. Indeed
the question “Which therapy is the most suitable for a certain patient at a certain
time?” is much more realistic. Here, we provide a brief overview of the objectively
measurable results of the three therapies to date and an outlook into future therapeutic
avenues.
