[Gene-based treatment in spinal muscular atrophy]

Abstract

Background: The 5q-associated spinal muscular atrophy (SMA) affects ~ 80-120 newborns annually. The disease is characterized by progressive paresis involving the bulbar and respiratory musculatures. The phenotypes are very heterogeneous ranging from severe courses with early death in the first years of life to loss of gait in older age.

Objective: There are now an increasing number of causally targeted therapies available that can either directly interfere with the transcription of the gene causing the disease or replace the homozygous loss of the SMN1 gene. This work aims to elucidate the current state of therapy in different groups of patients with SMA.

Material and methods: Presentation of clinical trials and basic studies with a focus on patients with disease onset in adulthood.

Results: The clinical studies all show improvement or stabilization of motor function; however, in individual cases, the burden of the therapy for severely immobilized patients must be considered in addition to the efficacy in the treatment decision. Even if the drugs show a good safety profile, observations on the long-term efficacy and safety of the new substance classes are still lacking.

Conclusion: The study landscape shows a good efficacy of the currently approved therapies across all degrees of severity and age groups. Due to the lack of comparative studies, the decision on the appropriate therapy should therefore be made according to an individual risk-benefit assessment.

Keywords: Gene therapy; Nusinersen; Onasemnogene; Risdiplam; SMN.