Therapie der spinalen Muskelatrophie mit dem Antisense-Oligonukleotid Nusinersen

Zusammenfassung

Die spinale Muskelatrophie ist eine genetische Motoneuronerkrankung, die sich im Kindes- und Jugendalter manifestiert und zu einer progredienten Muskelatrophie und Muskelschwäche führt. Anhand der klinischen Symptome, deren zeitlichen Auftretens sowie dem Erreichen motorischer Meilensteine wird die Erkrankung in drei unterschiedliche Typen eingeteilt. Klinisch am schwersten betroffen sind dabei Patienten mit Typ I (Werdnig-Hoffmann), der am häufigsten auftritt und mit einer deutlich verminderten Lebenserwartung einhergeht. Bislang standen für die Behandlung der spinalen Muskelatrophie lediglich symptomatische Maßnahmen zur Verfügung. Seit Juni 2017 ist nun jedoch die Therapie der spinalen Muskelatrophie mit dem Antisense- Oligonukleotid Nusinersen (Spinraza^®) für alle 5q-assoziierten Erkrankungen in Deutschland zugelassen. In dem folgenden Artikel gehen wir nach Darstellung der klinischen Symptome und Pathogenese der spinalen Muskelatrophie auf die Literatur zur Behandlung mit Nusinersen ein und diskutieren darüber hinaus die Herausforderungen bei der Behandlung von Jugendlichen und Erwachsenen mit spinaler Muskelatrophie mit dem Antisense-Oligonukleotid.

Summary

Spinal muscular atrophy is a genetic motor neuron disease of childhood and adolescence that leads to progressive muscular atrophy and muscle weakness. Based on clinical symptoms, the age of onset and the achievement of motor milestones, the disorder can be characterized in 3 subtypes. Type I disease (Werdnig-Hoffmann) is the most severe and common type accompanied by a significantly reduced life span. The standard of care for patients consisted in solely symptomatic treatment options so far. In June 2017, the antisense oligonucleotide nusinersen (Spinra^®) has been approved for all 5q-associated diseases in Germany. Beyond the clinical symptoms and pathogenetic pathways of spinal muscular atrophy, we provide an overview of the recent literature regarding the drug nusinersen and discuss the potential challenges in the treatment in adolescents and adults with this antisense oligonucleotide.

Schlüsselwörter

Spinale Muskelatrophie - Antisense-Oligonukleotide - Nusinersen

Keywords

Spinal muscular atrophy - antisense oligonucleotides - nusinersen

• Literatur

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