Therapie und Monitoring neuromuskulärer Repeat-Erkrankungen

Zusammenfassung

Repeat-Erkrankungen sind hereditäre durch pathologische Expansionen sich wiederholender Triplettoder Multiplett-DNA-Sequenzen (Repeats) hervorgerufene, in der Regel multisystemische Erkrankungen. Bevorzugt das neuromuskuläre System betreffen die myotonen Dystrophien Typ 1 und 2 (DM 1, 2), die okulopharyngeale Muskeldystrophie (OPMD), die spinobulbäre Muskelatrophie (SBMA, auch Kennedy-Syndrom) und eine Form der ALS, die durch Repeat-Expansionen im C9ORF72-Gen verursacht wird. Zunehmendes Verständnis der molekularen Pathogenese dieser Erkrankungen bildet die Grundlage für neue kausale Therapiestrategien, die sich überwiegend noch im präklinischen Stadium befinden oder in ersten klinischen Studien getestet werden. Das Monitoring und die Therapie von neurologischen und internistischen Symptomen (wie respiratorischer Insuffizienz oder kardialer Mitbeteiligung) erfordert eine interdisziplinäre Betreuung.

Summary

Repeat diseases are hereditary often multisystemic disorders caused by pathological expansions of repeated DNA sequences. The neuromuscular system is predominantly affected in myotonic dystrophy type 1 and 2 (DM1 and 2), oculopharyngeal muscular dystrophy (OPMD), spinal and bulbar muscle atrophy (SBMA, Kennedy’s disease) and a variant of amyotrophophic lateral sclerosis (ALS) caused by repeat expansions in the C9ORF72 gene. Increasing knowledge of the molecular pathogenesis has paved the way for novel therapeutic strategies which are currently subject of preclinical and first clinical studies. Monitoring and therapy of neurological and non-neurological symptoms (e.g . respiratory insufficiency or cardiac involvement) often require interdisciplinary treatment.

Schlüsselwörter

Myotone Dystrophie - okulopharyngeale Muskeldystrophie - spinobulbäre Muskelatrophie - ALS - symptomatische Therapie

Myotonic dystrophy - oculopharyngeal muscular dystrophy - spinal and bulbar muscle atrophy - amyotrophic lateral sclerosis - symptomatic therapy

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