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Neurotherapeutic effects of novel HO-1 inhibitors in vitro and in a transgenic mouse model of Alzheimer's disease

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2014
Contact PI Name:
Ajay Gupta
Contact PI Affiliation:
Department of Oncology, McGill University, Montreal, Quebec, Canada
Co-Authors:
B. Lacoste, P.J. Pistell, D.K. Ingram, E. Hamel, M.A. Alaoui-Jamali, W.A. Szarek, J.Z. Vlahakis, S. Jie, W. Song, H.M. Schipper
Primary Reference (PubMED ID):
25111043
Funding Source:
Institute for the Study of Aging (ISOA)
Alzheimer Society of Canada
Study Goal and Principal Findings:

The goal of this study was to examine the therapeutic effects of a series (QC-47, QC-56, and OB-28) of potent,selective novel azole-based, competitive and reversible HO-1 inhibitors on the AD-associated behavioral and pathological deficits in APPswe/PS1ΔE9 mice. QC-47, QC-56, and OB-28 significantly attenuated oxidative damage in astrocytes transfected with the HMOX gene. OB-28 treatement was found to significantly counter behavioral deficits and neuropathological alterations in the transgenic mice. More specifically, OB-28 was found to attenuate oxidative damage, beta amyloid pathology and astrogliosis. 

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
OB-28
PubMed
Patents
Therapeutic Target:
Heme Oxygenase 1
Open Targets
Pharos
Agora

Animal Model

Model Information:
Species:
Mouse
Model Type:
APPxPS1
Model Name:
APPswe/PSEN1dE9 (C57BL6)
ALZFORUM
Strain/Genetic Background:
C57BL/6J

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
Experiment Notes

PK profile is reported in the Supplementary Material

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Stone T Maze
Contextual Fear Conditioning
Histopathology
beta Amyloid Load
Dense-core/Compact Plaques
Biochemical
Oxidative Stress Markers
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Heme Oxygenase 1 (HO1)
Immunochemistry
Activated Astrocytes
Activated Microglia
Pharmacokinetics
Cmax
Area Under the Curve (AUC)
t1/2 (Elimination Half-Life)
Tmax
Toxicology
Body Weight
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