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A novel Alzheimer’s disease drug candidate targeting inflammation and fatty acid metabolism


Year of Publication:
Contact PI Name:
David Schubert
Contact PI Affiliation:
Cellular Neuroendocrinology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, USA
Daniel Daugherty, Joshua Goldberg, Wolfgang Fischer, Richard Dargusch, Pamela Maher
Primary Reference (PubMED ID):
Funding Source:
California Institute for Regenerative Medicine (CIRM)
Templeton Foundation
National Institute on Aging (NIA)
Study Goal and Principal Findings:

CAD-31 is an Alzheimer’s disease (AD) drug candidate that was selected on the basis of its ability to stimulate the replication of human embryonic stem cell-derived neural precursor cells as well as in APPswe/PS1ΔE9 AD mice. To move CAD-31 toward the clinic, experiments were undertaken to determine its neuroprotective and pharmacological properties, as well as to assay its therapeutic efficacy in a rigorous mouse model of AD. CAD-31 has potent neuroprotective properties in six distinct nerve cell assays that mimic toxicities observed in the old brain. Pharmacological and preliminary toxicological studies show that CAD-31 is brain-penetrant and likely safe. When fed to old, symptomatic APPswe/PS1ΔE9 AD mice starting at 10 months of age for 3 additional months in a therapeutic model of the disease, there was a reduction in the memory deficit and brain inflammation, as well as an increase in the expression of synaptic proteins. Small-molecule metabolic data from the brain and plasma showed that the major effect of CAD-31 is centered on fatty acid metabolism and inflammation. Pathway analysis of gene expression data showed that CAD-31 had major effects on synapse formation and AD energy metabolic pathways. All of the multiple physiological effects of CAD-31 were favorable in the context of preventing some of the toxic events in old age-associated neurodegenerative diseases.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported
Model Type:
Strain/Genetic Background:
Not Applicable

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
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


Outcome Measured
Outcome Parameters
Morris Water Maze
Elevated Plus Maze
Fear Conditioning Response
Activity-Regulated Cytoskeleton-Associated Protein (Arc)
Eukaryotic Translation Initiation Factor 2 alpha (eIF2 alpha)
phospho-Eukaryotic Translation Initiation Factor 2 alpha (phospho-eIF2 alpha)
AMP-Activated Protein Kinase (AMPK)
phospho-AMP-Activated Protein Kinase (phospho-AMPK)
Vascular Cell Adhesion Molecule (VCAM)
Receptor for Advanced Glycation Endproducts (RAGE)
Oligomycin Sensitivity-Conferring Protein (OSCP)
Doublecortin (DCX)
phospho-Acetyl-Coenzyme A Carboxylase (phospho-ACC)
Brain-beta Amyloid Peptide 42
Drug Concentration-Serum
Drug Concentration-Brain
Blood Brain Barrier Penetration
Body Weight
Food Intake
hERG Assay
Ames Test
CYP Induction