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2013 | 13 | 4 | 287–294
Article title

Farmakoterapia dysfunkcji poznawczych w chorobie Alzheimera: obecne strategie i terapie eksperymentalne

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Pharmacotherapy of cognitive dysfunctions in Alzheimer’s disease: current strategies and experimental therapies
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Abstracts
EN
Currently available methods of pharmacological treatment of cognitive dysfunction related to Alzheimer’s dis­ease (AD) are based on augmentation of cholinergic neurotransmission (by inhibiting activity of cholinesterases) or modulation of glutamatergic transmission (by acting on NMDA receptor). Both classes of drug exhibit clinically significant (though modest) symptomatic improvement not only considering cognition but also behaviour and ac­tivities of daily living. Whether or not they modify natural course of the disease, is not clearly confirmed by result of rigorously planned clinical trials and is currently considered unlikely. With the development of genetic and molecu­lar studies on the pathogenesis of AD novel treatment targets emerged recently, importantly these based on amyloid cascade hypothesis and τ protein phosphorylation. Unfortunately, the so far undertaken clinical trials yielded dis­appointing results, either proving not be effective or showing unfavourable side effects profile. The most commonly proposed explanations of these failures include starting trials too late during the disease process and/or insufficiently specific strategies of patients’ selection resulting in inclusion of subjects suffering from other than AD cognitive dys­functions. Biomarkers of disease-specific process are currently leading answer to the experienced trials failures as they are starting to be routinely used in novel studies.
PL
Obecnie dostępne metody farmakologicznego leczenia zaburzeń funkcji poznawczych w chorobie Alzheimera (Alzheimer’s disease, AD) opierają się na potencjalizacji przekaźnictwa cholinergicznego (inhibitory cholinesteraz) oraz modulowaniu przekaźnictwa glutaminianergicznego (memantyna). Leki te wywierają zauważalny efekt objawo­wy w zakresie nie tylko funkcji poznawczych, lecz także zachowania i codziennej aktywności. Ich wpływ na naturalny przebieg choroby nie został jak dotąd jednoznacznie potwierdzony i ze względu na mechanizm działania jest uwa­żany za mało prawdopodobny. Wraz z rozwojem badań genetycznych i molekularnych nad patogenezą AD do prób klinicznych wchodzą leki, które mają bezpośrednio oddziaływać na procesy odpowiedzialne za neurodege­nerację i prowadzące do neurotoksycznego działania oligomerów i odkładania się w mózgu złogów białkowych. Niestety, przeprowadzone dotąd badania kliniczne zawiodły oczekiwania – nie potwierdziły skuteczności klinicz­nej i/lub wskazały na problemy z bezpieczeństwem leczenia. Najczęściej wymienianymi przyczynami tych niepo­wodzeń mają być podawanie leków w zbyt późnym stadium choroby i/lub niewystarczająco selektywne strategie doboru pacjentów, skutkujące włączaniem do badań chorych cierpiących na inne niż AD przyczyny zaburzeń po­znawczych. Proponowaną odpowiedzią na niepowodzenia prób klinicznych ma być inkorporowanie biomarkerów procesu chorobowego do nowych badań.
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13
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4
Pages
287–294
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References
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