β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease

Alzheimer’s disease (AD) and vascular dementia are responsible for up to 90% of dementia cases. According to the World Health Organization (WHO), a staggering number of 35.6 million people are currently diagnosed with dementia. Blocking disease progression or preventing AD altogether is desirable fo...

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Main Authors:	Menting, Kelly Willemijn, Claassen, Jurgen A. H. R.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104928/

id	pubmed-4104928
recordtype	oai_dc
spelling	pubmed-41049282014-08-06 β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease Menting, Kelly Willemijn Claassen, Jurgen A. H. R. Neuroscience Alzheimer’s disease (AD) and vascular dementia are responsible for up to 90% of dementia cases. According to the World Health Organization (WHO), a staggering number of 35.6 million people are currently diagnosed with dementia. Blocking disease progression or preventing AD altogether is desirable for both social and economic reasons and recently focus has shifted to a new and promising drug: the β-secretase inhibitor. Much of AD research has investigated the amyloid cascade hypothesis, which postulates that AD is caused by changes in amyloid beta (Aβ) stability and aggregation. Blocking Aβ production by inhibiting the first protease required for its generation, β-secretase/BACE1, may be the next step in blocking AD progression. In April 2012, promising phase I data on inhibitor MK-8931 was presented. This drug reduced Aβ cerebral spinal fluids (CSF) levels up to 92% and was well tolerated by patients. In March 2013 data was added from a one week trial in 32 mild to moderate AD patients, showing CSF Aβ levels decreased up to 84%. However, β-site APP cleaving enzyme 1 (BACE1) inhibitors require further research. First, greatly reducing Aβ levels through BACE1 inhibition may have harmful side effects. Second, BACE1 inhibitors have yet to pass clinical trial phase II/III and no data on possible side effects on AD patients are available. And third, there remains doubt about the clinical efficacy of BACE1 inhibitors. In moderate AD patients, Aβ plaques have already been formed. BACE1 inhibitors prevent production of new Aβ plaques, but hypothetically do not influence already existing Aβ peptides. Therefore, BACE1 inhibitors are potentially better at preventing AD instead of having therapeutic use. Frontiers Media S.A. 2014-07-21 /pmc/articles/PMC4104928/ /pubmed/25100992 http://dx.doi.org/10.3389/fnagi.2014.00165 Text en Copyright © 2014 Menting and Claassen. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Menting, Kelly Willemijn Claassen, Jurgen A. H. R.
spellingShingle	Menting, Kelly Willemijn Claassen, Jurgen A. H. R. β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease
author_facet	Menting, Kelly Willemijn Claassen, Jurgen A. H. R.
author_sort	Menting, Kelly Willemijn
title	β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease
title_short	β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease
title_full	β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease
title_fullStr	β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease
title_full_unstemmed	β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease
title_sort	β-secretase inhibitor; a promising novel therapeutic drug in alzheimer’s disease
description	Alzheimer’s disease (AD) and vascular dementia are responsible for up to 90% of dementia cases. According to the World Health Organization (WHO), a staggering number of 35.6 million people are currently diagnosed with dementia. Blocking disease progression or preventing AD altogether is desirable for both social and economic reasons and recently focus has shifted to a new and promising drug: the β-secretase inhibitor. Much of AD research has investigated the amyloid cascade hypothesis, which postulates that AD is caused by changes in amyloid beta (Aβ) stability and aggregation. Blocking Aβ production by inhibiting the first protease required for its generation, β-secretase/BACE1, may be the next step in blocking AD progression. In April 2012, promising phase I data on inhibitor MK-8931 was presented. This drug reduced Aβ cerebral spinal fluids (CSF) levels up to 92% and was well tolerated by patients. In March 2013 data was added from a one week trial in 32 mild to moderate AD patients, showing CSF Aβ levels decreased up to 84%. However, β-site APP cleaving enzyme 1 (BACE1) inhibitors require further research. First, greatly reducing Aβ levels through BACE1 inhibition may have harmful side effects. Second, BACE1 inhibitors have yet to pass clinical trial phase II/III and no data on possible side effects on AD patients are available. And third, there remains doubt about the clinical efficacy of BACE1 inhibitors. In moderate AD patients, Aβ plaques have already been formed. BACE1 inhibitors prevent production of new Aβ plaques, but hypothetically do not influence already existing Aβ peptides. Therefore, BACE1 inhibitors are potentially better at preventing AD instead of having therapeutic use.
publisher	Frontiers Media S.A.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104928/
_version_	1613116041391505408

β-secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease

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