Von der symptomatischen zur kausalen Therapie?

Zusammenfassung

Die gegenwärtige Pharmakotherapie der Alzheimer-Demenz (AD) zielt auf die Verbesserung oder Stabilisierung von kognitiver Leistungsfähigkeit und Alltagsaktivitäten, auf eine Verminderung des Auftretens oder eine Reduktion von nicht kognitiven, neuropsychiatrischen Symptomen sowie auf eine Verzögerung der Progression. Zur medikamentösen Behandlung sind diesymptomatisch wirksamen Acetylcholinesterase-Inhibitoren (ACh-I) Donepezil, Galantamin und Rivastigmin sowie der partielle N-Methyl-D-Aspartat-(NMDA)-Antagonist Memantine zugelassen. Neue symptomatisch wirksame Substanzen wie selektive Acetylcholinrezeptor-modulierende Pharmaka oder Histaminrezeptorantagonisten befinden sich gegenwärtig in der Entwicklung. Obwohl krankheitsmodifizierende, kausale Therapien derzeit noch nicht verfügbar sind, gibt es auf den unterschiedlichen Stufen der pharmakologischen Prüfung eine Reihe von Neuentwicklungen, darunter Substanzen, die direkt auf bekannte Pathomechanismen der AD wirken, insbesondere den amyloidogenen Stoffwechselweg der Amyloidvorläufer-Protein-Prozessierung (APP-Prozessierung). Leider konnte trotz präklinisch überzeugender Hinweise auf Wirksamkeit verschiedener Ansätze bisher der klinische Durchbruch bei der „kausalen” pharmakologischen Therapie der AD nicht erreicht werden. Mehrere im Tierversuch erfolgreiche und vielversprechende krankheitsmodifizierende Substanzen fielen jüngst bei der klinischen Prüfung am Patienten durch. Die vorliegende Übersichtsarbeit fasst bewertend die etablierten und insbesondere die neuen und zukünftigen pharmakologischen Therapieoptionen zusammen.

Abstract

Until today the pharmacological therapy of Alzheimer’s disease (AD) is still limited to symptomatic temporary improvement or stabilization of cognitive performance and activities of daily living, and the reduction of neuropsychiatric symptoms of the disease. Available symptomatic treatment options are the acetylcholinesterase inhibitors (ACh-I) donepezil, galantamine, rivastigmine, and the partial N-Methyl-D-Aspartat-(NMDA)-antagonist memantine. Further substances with symptomatic targets, especially selective acetylcholine and histamine receptors, are currently under development. Numerous of disease-modifying substances mainly targeting components of the amyloidogenic pathway of AD are presently studied in different phases of preclinical and clinical trials. Against earlier expectations which derived from promising preclinical immunization studies the breakthrough of disease-modification in AD is not in sight yet. Aim of this review is to summarize established pharmacological treatment options and the stage of development of upcoming symptomatic and disease-modifying substances of AD.

Alzheimer Demenz - Pharmakotherapie - symptomatisch - krankheitsmodifizierend

Alzheimer’s Disease - pharmacotherapy - symptomatic - disease-modifying

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