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Simvastatin enhances immune responses to Aβ vaccination and attenuates vaccination-induced behavioral alterations

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2010
Contact PI Name:
Ken-ichiro Fukuchi
Contact PI Affiliation:
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Illinois, USA
Co-Authors:
Jinghong Kou, Hong-Duck Kim, JingJi Jin, Dongfeng Cao, Ling Li, Robert Lalonde
Primary Reference (PubMED ID):
20691674
Funding Source:
National Institute on Aging (NIA)
Alzheimer's Association
Study Goal and Principal Findings:

In this study the authors tested the efficacy of the combined treatment of an adenovirus DNA vaccine, AdPEDI-(Aβ1-6)11, with simvastatin on immune funtion and behavior in young C57BL/6 mice. The results showed that simvastatin significantly increased the number of the mice responding to vaccination compared with the mice receiving only AdPEDI-(Aβ1-6)11. Immunoglobulin isotyping revealed that the vaccination predominantly induced Th2 immune responses. Simvastatin treatment prevented Aβ-induced production of IFN-γ in splenocytes.   AdPEDI-(Aβ1-6)11 treatment altered mouse behavior in T- and elevated plus-maze tests and simvastatin counteracted such behavioral changes. These results indicate that simvastatin clearly enhances the immune responses of C57BL/6 mice to the nasal vaccination with AdPEDI-(Aβ1-6)11. Simvastatin may be effective in preventing behavioral changes associated with vaccination.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Simvastatin
PubMed
PubChem
DrugBank
ClinicalTrials
Patents
Therapeutic Target:
HMG-CoA Reductase
Open Targets
Pharos
Agora
Therapy Type:
Biologic - Immunotherapy(active)
Therapeutic Agent:
AdPEDI-(Abeta 1-6)11 (AAV Encoding 11 Tandem Repeats of Abeta1-6)
PubMed
ClinicalTrials
Patents
Therapeutic Target:
beta Amyloid Peptide
Open Targets
Pharos
Agora
Therapeutic Notes:
AdPEDI-Aβ(1-6)11, was prepared as previously described: Kim HD, Maxwell JA, Kong FK, Tang DC, Fukuchi K. Induction of anti-inflammatory immune response by an adenovirus vector encoding 11 tandem repeats of Abeta1-6: toward safer and effective vaccines against Alzheimer's disease. Biochem Biophys Res Commun. 2005; 336:84–92 [PubMed: 16126169].

Animal Model

Model Information:
Species:
Mouse
Model Type:
Non-transgenic
Strain/Genetic Background:
C57BL/6

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
T Maze
Morris Water Maze
Open Field Test
Elevated Plus Maze
Motor Function
Balance Beam Test
Coat Hanger Test
Biochemical
Plasma-Total Cholesterol
Cytokines
Immunology
Anti-beta Amyloid Antibody Titers
Anti-beta Amyloid Antibody Isotypes
Interferon (IFN) gamma Production
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