Spinale Muskelatrophie im Erwachsenenalter

Die 5q-assoziierte spinale Muskelatrophie (SMA) ist eine fortschreitende autosomal rezessive Motoneuronerkrankung mit einer Inzidenz von 1:11 000 Lebendgeburten, die durch den Verlust des Survival Motor Neuron 1-Gens (SMN1) verursacht wird [1]. Additiv zur bisherigen multidisziplinären supportiven pulmonalen, gastroenterologischen, orthopädischen, neuropädiatrischen und neuromuskulären Behandlung wurden in den letzten Jahren 3 bahnbrechende erkrankungsmodifizierende Therapien der 5q-assoziierten spinalen Muskelatrophie (SMA) zugelassen, die Phänotypen und Therapielandschaft entscheidend verändert und damit neue Standards für die Beeinflussung von Neurodegeneration ermöglicht haben: Nusinersen/Spinraza als Antisense-Oligonukleotidtherapie, Onasemnogene abeparvovec/Zolgensma als eine AAV9-basierte Genersatztherapie, und Risdiplam/Evrysdi als ein „small Molecule Modifier“ des pre-mRNA Splicings.

Abstract

5q spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease affecting 1: 11000 live births and ranging from intrauterine to early adult onset. The course of the disease is progressive, the phenotype varies within a disease continuum and is mainly determined by the SMN2 copy number. So far, three disease modifying treatments (Nusinersen/Spinraza, Onasemnogene abeparvovec/Zolgensma, Risdiplam/Evrysdi) have been approved; however, gene replacement therapy with Onasemnogen abeparvovec is mainly applied from birth to toddler age. SMA treatment requires a multidisciplinary management in specialized neuromuscular centers. Since October 2021, SMA is part of the newborn screening in Germany. When SMA is clinically suspected, timely genetic diagnostics is crucial for a rapid start of treatment, since „time is motor neuron“. The different therapeutic options must be discussed with patients and families, and patient expectations must be managed. Assessment of long-term data in disease-specific registries is highly encouraged world-wide and mandatory in Germany.

Schlüsselwörter

spinale Muskelatrophie - erkrankungsmodifizierende Therapie - Neugeborenenscreening

Key words

spinal muscular atrophy - disease-modifying therapy - newborn screening

Publication History

Article published online:
14 September 2022

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