Therapeutic strategies for Alzheimer's disease in clinical trials

摘要: Alzheimer's disease (AD) is considered to be the most common cause of dementia and an incurable, progressive neurodegenerative disorder. Current treatment disease, essentially symptomatic, based on three cholinesterase inhibitors memantine, affecting glutamatergic system. Since 2003, no new drugs have been approved for AD. This article presents current directions in search novel, potentially effective agents AD, as well selected promising strategies. These include acting upon beta-amyloid, such vaccines, antibodies or modulators γ- β-secretase; directed against tau protein compounds antagonists neurotransmitter systems (serotoninergic 5-HT6 histaminergic H3). Ongoing clinical trials with Aβ (solanezumab, gantenerumab, crenezumab) seem promising, while vaccines (AADvac1 ACI-35) are now early-stage trials. Interesting results also achieved involving small molecules β-secretase (MK-8931, E2609), a combination antagonist (idalopirdine) donepezil, inhibition advanced glycation end product receptors by azeliragon modulation acetylcholine response α-7 nicotinic encenicline. Development central nervous system usually difficult time-consuming process, case AD to-date had very high failure rate. Most phase II ending positive outcome do not succeed III, often due serious adverse effects lack therapeutic efficacy.