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Therapeutic strategies for Alzheimer's disease in clinical trials
- Source :
- Pharmacological reports : PR. 68(1)
- Publication Year :
- 2015
-
Abstract
- Alzheimer's disease (AD) is considered to be the most common cause of dementia and is an incurable, progressive neurodegenerative disorder. Current treatment of the disease, essentially symptomatic, is based on three cholinesterase inhibitors and memantine, affecting the glutamatergic system. Since 2003, no new drugs have been approved for treatment of AD. This article presents current directions in the search for novel, potentially effective agents for the treatment of AD, as well as selected promising treatment strategies. These include agents acting upon the beta-amyloid, such as vaccines, antibodies and inhibitors or modulators of γ- and β-secretase; agents directed against the tau protein as well as compounds acting as antagonists of neurotransmitter systems (serotoninergic 5-HT6 and histaminergic H3). Ongoing clinical trials with Aβ antibodies (solanezumab, gantenerumab, crenezumab) seem to be promising, while vaccines against the tau protein (AADvac1 and ACI-35) are now in early-stage trials. Interesting results have also been achieved in trials involving small molecules such as inhibitors of β-secretase (MK-8931, E2609), a combination of 5-HT6 antagonist (idalopirdine) with donepezil, inhibition of advanced glycation end product receptors by azeliragon or modulation of the acetylcholine response of α-7 nicotinic acetylcholine receptors by encenicline. Development of new effective drugs acting upon the central nervous system is usually a difficult and time-consuming process, and in the case of AD to-date clinical trials have had a very high failure rate. Most phase II clinical trials ending with a positive outcome do not succeed in phase III, often due to serious adverse effects or lack of therapeutic efficacy.
- Subjects :
- 0301 basic medicine
tau Proteins
Idalopirdine
Pharmacology
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
medicine
Animals
Humans
Solanezumab
Donepezil
Encenicline
Clinical Trials as Topic
Amyloid beta-Peptides
Memantine
General Medicine
medicine.disease
030104 developmental biology
Crenezumab
Cholinesterase Inhibitors
Alzheimer's disease
Amyloid Precursor Protein Secretases
Gantenerumab
Psychology
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 22995684
- Volume :
- 68
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Pharmacological reports : PR
- Accession number :
- edsair.doi.dedup.....83cad20c2bf907b2648fc3a6c2ca9f5b