Novel Intervention for Amyloid-Induced Neuroinflammation

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41AG028198-01A1
Agency Tracking Number: AG028198
Amount: $263,420.00
Phase: Phase I
Program: STTR
Awards Year: 2007
Solicitation Year: 2007
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
COGNOSCI, INC., 79 T. W. Alexander Drive, RESEARCH TRIANGLE PARK, NC, 27709
DUNS: 141881727
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: Y
Principal Investigator
 (919) 765-0028
Business Contact
Phone: (919) 765-0028
Research Institution
 Nonprofit college or university
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 Aa 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 sequence 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 dementia 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/Iowa 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 overall 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-inflammatory 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 treatment 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 in 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 COG133, 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

* Information listed above is at the time of submission. *

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