[Personalized treatment options for spinal muscular atrophy].

Abstract

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. 

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