Drug candidates in clinical trials for Alzheimer's disease
Journal
Journal of Biomedical Science
Journal Volume
24
Journal Issue
1
Pages
47
Date Issued
2017
Author(s)
Hung S.-Y.
Abstract
Alzheimer's disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation. The lowered concentrations of acetylcholine (ACh) in AD result in a progressive and significant loss of cognitive and behavioral function. Current AD medications, memantine and acetylcholinesterase inhibitors (AChEIs) alleviate some of these symptoms by enhancing cholinergic signaling, but they are not curative. Since 2003, no new drugs have been approved for the treatment of AD. This article focuses on the current research in clinical trials targeting the neuropathological findings of AD including acetylcholine response, glutamate transmission, Aβ clearance, tau protein deposits, and neuroinflammation. These investigations include acetylcholinesterase inhibitors, agonists and antagonists of neurotransmitter receptors, β-secretase (BACE) or γ-secretase inhibitors, vaccines or antibodies targeting Aβ clearance or tau protein, as well as anti-inflammation compounds. Ongoing Phase III clinical trials via passive immunotherapy against Aβ peptides (crenezumab, gantenerumab, and aducanumab) seem to be promising. Using small molecules blocking 5-HT6 serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials. We here systemically review the findings from recent clinical trials to provide a comprehensive review of novel therapeutic compounds in the treatment and prevention of AD. ? 2017 The Author(s).
Subjects
Alzheimer's disease; Clinical trials; Drug treatment; Neurodegenerative disease
SDGs
Other Subjects
5,6 dihydro 2 imino 3 methyl 6 [4 [5 (1 propynyl) 3 pyridinyl] 2 thienyl] 4 pyrimidinone; abt 288; Alzheimer disease vaccine; avagacestat; bapineuzumab; beta secretase inhibitor; bi 1181181; cholinesterase inhibitor; donepezil; encenicline; epothilone D; evp 0962; galantamine; gamma secretase inhibitor; gsk 239512; histamine H3 receptor antagonist; idalopirdine; intepirdine; ly 2811376; ly 2886721; memantine; placebo; rg 7129; riluzole; rivastigmine; semagacestat; suvn g 3031; tacrine; unclassified drug; unindexed drug; vanutide cridificar; monoclonal antibody; adjuvant therapy; Alzheimer disease; amino acid transport; amyotrophic lateral sclerosis; brain hemorrhage; cholinergic nerve cell; clinical trial (topic); cognitive defect; drug approval; drug bioavailability; drug efficacy; drug mechanism; drug penetration; drug research; drug safety; drug targeting; drug tolerability; excitotoxicity; gastrointestinal symptom; glucosuria; human; immunotherapy; liver toxicity; meningoencephalitis; microtubule assembly; nervous system inflammation; neurofibrillary tangle; neuropathology; neuroprotection; non melanoma skin cancer; nonhuman; phase 1 clinical trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); priority journal; protein phosphorylation; Review; schizophrenia; systematic review; Alzheimer disease; Alzheimer Disease; Antibodies, Monoclonal; Clinical Trials as Topic; Immunotherapy
Type
review