Aktuelles zur Charcot-Marie-Tooth-Erkrankung

ZUSAMMENFASSUNG

Die Charcot-Marie-Tooth-Erkrankung (CMT) ist die häufigste hereditäre Neuropathie (Prävalenz 1:2500) mit über 90 assoziierten Genen. Der häufigste Subtyp (CMT1A), assoziiert mit einer Duplikation des peripheren Myelinprotein-22-Gens (PMP22) ist Ursache für 40–50 % aller Fälle. Klinische Zeichen sind distal symmetrische Paresen, Atrophien, Sensibilitätsstörungen, Fußdeformitäten und Areflexie. Validierte Skalen zur Evaluation der Beeinträchtigung (CMTNS2, ONLS, 9-hole-pegtest, Gehtestungen) sind verfügbar und molekulare Biomarker aus Blut und Hautbiopsien wurden validiert. Therapieoptionen im Entwicklungsstadium sind das Gen-Silencing (Minderung der Überexpression von PMP22), Sekretasen zur Regulierung der Neuregulinaktivität mit Einfluss auf Meylindicke und Funktion sowie Inhibitoren des Kalziuminfluxes in Schwannzellen. PXT3003 (Sorbitol, Naltrexon, Baclofen) wurde im Tiermodell erfolgreich getestet. Ein möglicher Therapieansatz mittels Substitution des Fettmoleküls Lecithin konnte in CMT1A-Ratten die Muskelkraft und die Anzahl myelinisierter Axone erhöhen.

ABSTRACT

Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy (prevalence 1: 2500) with over 90 associated genes. The most common subtype (CMT1A) associated with a duplication of the peripheral myelin protein-22 gene (PMP22) is responsible for 40–50 % of all cases. Clinical signs are distally symmetrical paresis, muscle atrophies, sensory dysfunktion, foot deformities and areflexia. Validated scores (CMTNS2, ONLS, 9-hole-peg-test, walking tests) are available and molecular biomarkers from blood and skin samples have been validated. Developmental therapy options include gene silencing to reduce overexpression of PMP22, secretases to regulate neuregulin activity affecting the myelin thickness and function and inhibitors of calcium influx in Schwann cells.PXT3003 (sorbitol, naltrexone, baclofen) has been tested in an animal model. Substitution of the fat molecule lecithin increased muscle strength and the number of myelinated axons in CMT1A rats.

Schlüsselwörter

Charcot-Marie-Tooth - Neurogenetik - Hereditäre Neuropathie - Biomarker

Key words

Charcot-Marie-Tooth - neurogenetics - hereditary neuropathy - biomarker

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