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Novel Intervention for Amyloid-Induced Neuroinflammation

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
85221
Program Year/Program:
2007 / STTR
Agency Tracking Number:
AG028198
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
COGNOSCI, INC.
79 T. W. Alexander Drive RESEARCH TRIANGLE PARK, NC 27709-2076
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2007
Title: Novel Intervention for Amyloid-Induced Neuroinflammation
Agency: HHS
Contract: 1R41AG028198-01A1
Award Amount: $263,420.00
 

Abstract:

DESCRIPTION (provided by applicant): Novel Intervention for Amyloid-Induced Neuroinflammation Extracellular deposition of the amyloid a-protein (Aa) in brain is a prominent pathological feature of Alzheimer's disease (AD) and related disorders. Fibrillar A a deposition in the cerebral vasculature, a condition known as cerebral amyloid angiopathy (CAA), is also commonly found in AD. Additionally, several familial monogenic forms of CAA exist that result from mutations that reside within the Aa peptide sequenc e of AaPP gene. These include Dutch-type (E22Q) and Iowa-type (D23N) mutations which cause early and severe cerebral vascular amyloid deposition. Recent studies have implicated cerebral microvascular Aa deposition in promoting neuroinflammation and dementi a in patients with CAA. Cerebral microvascular, but not parenchymal, amyloid deposition is more often correlated with dementia in individuals afflicted with AD and CAA. Recently, we generated novel transgenic mice that express human vasculotropic Dutch/Iow a mutant amyloid a-protein precursor (AaPP) in brain, designated Tg-SwDI, that develop early-onset and extensive fibrillar cerebral microvascular Aa deposition in the absence of parenchymal fibrillar plaque amyloid. More recent work from our laboratory has demonstrated that Tg-SwDI mice exhibit robust neuroinflammation that is strongly associated with the cerebral microvascular amyloid deposition. Furthermore, Tg-SwDI mice show marked deficits in behavioral performance. In light of these findings, the overa ll hypothesis that forms the basis for this proposal is that cerebral microvascular fibrillar Aa deposition promotes neuroinflammation in the absence of fibrillar plaque amyloid. The aim of the present proposal is to test the efficacy of a potent anti-infl ammatory compound, COG133, which is a novel peptide fragment of apolipoprotein E, for its ability to modulate microvascular amyloid, neuroinflammation and behavioral performance in these unique Tg-SwDI mice. Completion of these Phase 1 studies will provide proof of principle that a novel drug treatment may reduce cerebral microvascular amyloid-induced neuroinflammation, behavioral deficits and resulting pathology. Ultimately, if successful, this therapeutic regimen would represent a novel and effective trea tment for neuro-inflammation associated with amyloid deposition in Alzheimer's disease. Pr Novel Intervention for Amyloid-Induced Neuroinflammation Cerbrovascular deposits of fibrillar amyloid are known as Cerebral Amyloid Angiopathy or CAA. CAA is found i n greater than 97% of all autopsy confirmed cased of Alzheimer's disease (AD). CAA is also associated with robust activation of neuroinflammatory cells and the release of inflammatory cytokines like Interleukin-6 (IL-6). We have previously reported that CO G133, a novel anti-inflammatory peptide derived from apolipoprotein-E, could reduce IL-6 levels in the brains of whole animals. We now propose to test whether COG133 can reduce the inflammation found in the brains of Tg-SwDI mice that display prominent CAA and neuroinflamation. If COG133 can reduce the brain inflammation, it may also improve the behavioral performance of these animals. Pu

Principal Investigator:

Michael P. Vitek
9197650028
MIKEVITEK@COGNOSCI.COM

Business Contact:

Michael P. Vitek
mikevitek@cognosci.com
Small Business Information at Submission:

COGNOSCI, INC.
COGNOSCI, INC. 79 T. W. Alexander Drive RESEARCH TRIANGLE PARK, NC 27709

EIN/Tax ID: 562208520
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
STONY BROOK UNIVERSITY
STONY BROOK UNIVERSITY
STONY BROOK, NY 11794
RI Type: Nonprofit college or university