Farmakološke mogućnosti liječenja Alzheimerove bolesti

master's thesis

• Title (english): Pharmacological treatment options for Alzheimer disease
• Author: Marija Marković
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Iva Mucalo (član povjerenstva)
• Committee member: Sandra Šupraha-Goreta (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2024-08-30, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Cilj ovoga preglednog rada je prikazati terapijske mogućnosti liječenja Alzheimerove bolesti, kako simptomatske, tako i nove generacije lijekova koji utječu na tijek bolesti, zatim lijekove koji su procesu istraživanja, s naglaskom na kliničku fazu 3 te ostale dobro poznate lijekove koji su potencijalni kandidati za prenamjenu.
Alzheimerova bolest progresivna je neurodegenerativna bolest koja pogađa milijune ljudi diljem svijeta. Svojim napredovanjem dovodi do gubitka pamćenja, kognitivnog propadanja i promjena u ponašanju rezultirajući potpunom ovisnošću oboljele osobe o pružatelju skrbi. Ključne patofiziološke značajke ove bolesti su izvanstanično nakupljanje amiloidnih plakova i unutarstanično nakupljanje tau spletova, praćeno neuroupalom, neurodegeneracijom i atrofijom mozga.
Farmakološke mogućnosti liječenja Alzheimerove bolesti su ograničene. Usmjerene su većinom na ublažavanje postojećih simptoma bolesti i uključuju antagonist NMDA receptora memantin i inhibitore acetilkolinesteraze: donepezil, rivastigmin i galantamin. Međutim, brojnim kliničkim istraživanjima nastoji se pronaći odgovarajuća terapija koja će utjecati na osnovne patolfiziološke procese koji uzrokuju ili dovode do pogoršanja bolesti. Takvom terapijom mogla bi se zaustaviti ili usporiti progresija bolesti.
Američka Agencija za hranu i lijekove je odobrila tri biološka lijeka usmjerena na amiloidnu patologiju - adukanumab, lekanemab i donanemab. Ova tri monoklonska protutijela, iako su izazvala podijeljena mišljenja znanstvene zajednice, neosporivo su prekretnica u liječenju Alzheimerove bolesti.
Osim toga, jedan od pristupa u pronalaženju nove terapije uključuje prenamjenu postojećih lijekova, što može rezultirati značajnim financijskim i vremenskim uštedama.

Abstract (english)

This review summarizes fundamental information on Alzheimer's disease and aims to present currently available symptomatic treatment, disease-modifying therapy, potential targets for new drug development, potential future disease-modifying therapy with an emphasis on phase 3 of clinical trials, and drug repurposing candidates.
Alzheimer's disease is a progressive neurodegenerative disorder affecting millions of people worldwide. As it progresses, it leads to memory loss, cognitive decline, and behavioral changes, resulting in complete dependence of affected individuals on caregivers. Key pathophysiological features include extracellular accumulation of amyloid plaques and intracellular accumulation of tau tangles, accompanied by neuroinflammation, neurodegeneration, and brain atrophy.
Pharmacological treatment options for Alzheimer's disease are limited. They are mainly focused on alleviating existing symptoms and include NMDA receptor antagonist memantine and acetylcholinesterase inhibitors: donepezil, rivastigmine, and galantamine. However, numerous clinical studies aim to find the appropriate therapy that will impact the underlying biological processes that are causing or contributing to the worsening of the disease.
The US FDA has approved three new therapies targeting amyloid pathology: aducanumab, lecanemab and donanemab. Despite divided opinions within the scientific community, these three monoclonal antibodies present undeniably a breakthrough in the treatment of Alzheimer's disease.
There is also one additional approach in seeking new therapies and it involves repurposing existing drugs, which could lead to significant financial and time savings.

• Keywords: Alzheimerova bolest; antagonist NMDA receptora; demencija; imunoterapija; inhibitori acetilkolinesteraze; monoklonska protutijela; prenamjena lijekova; tau protein; β-amiloid
• Keywords (english): acetylcholinesterase inhibitors; Alzheimer's disease; dementia; drug repurposing; immunotherapy; monoclonal antibodies; NMDA receptor antagonist; tau protein; β-amyloid
• Language: croatian
• URN:NBN: urn:nbn:hr:163:534139
• Study programme: Title: Pharmacy - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar farmacije (sveučilišni magistar farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-11-22 12:23:08