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Biochem Pharmacol DOI:10.1016/j.bcp.2014.01.037

Building a pipeline to discover and validate novel therapeutic targets and lead compounds for Alzheimer's disease.

Publication TypeJournal Article
Year of Publication2014
AuthorsBennett, DA, Yu, L, De Jager, PL
JournalBiochem Pharmacol
Volume88
Issue4
Pages617-30
Date Published2014 Apr 15
ISSN1873-2968
KeywordsAlzheimer Disease, Chronic Disease, Drug Discovery, Genome-Wide Association Study, Humans, Models, Biological
Abstract

Cognitive decline, Alzheimer's disease (AD) and other causes are major public health problems worldwide. With changing demographics, the number of persons with dementia will increase rapidly. The treatment and prevention of AD and other dementias, therefore, is an urgent unmet need. There have been considerable advances in understanding the biology of many age-related disorders that cause dementia. Gains in understanding AD have led to the development of ante-mortem biomarkers of traditional neuropathology and the conduct of several phase III interventions in the amyloid-β cascade early in the disease process. Many other intervention strategies are in various stages of development. However, efforts to date have met with limited success. A recent National Institute on Aging Research Summit led to a number of requests for applications. One was to establish multi-disciplinary teams of investigators who use systems biology approaches and stem cell technology to identify a new generation of AD targets. We were recently awarded one of three such grants to build a pipeline that integrates epidemiology, systems biology, and stem cell technology to discover and validate novel therapeutic targets and lead compounds for AD treatment and prevention. Here we describe the two cohorts that provide the data and biospecimens being exploited for our pipeline and describe the available unique datasets. Second, we present evidence in support of a chronic disease model of AD that informs our choice of phenotypes as the target outcome. Third, we provide an overview of our approach. Finally, we present the details of our planned drug discovery pipeline.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0006-2952(14)00076-8
DOI10.1016/j.bcp.2014.01.037
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24508835?dopt=Abstract

Alternate JournalBiochem. Pharmacol.
PubMed ID24508835
PubMed Central IDPMC4054869
Grant ListU01 AG046152 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01AG17917 / AG / NIA NIH HHS / United States
R01 AG036042 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
RC2 AG036547 / AG / NIA NIH HHS / United States
R01AG15819 / AG / NIA NIH HHS / United States
P30AG10161 / AG / NIA NIH HHS / United States
R01 AG036836 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States