Skip to main content
U.S. flag

An official website of the United States government

A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2015
Contact PI Name:
Ulf Neumann
Contact PI Affiliation:
Neuroscience, Novartis Institutes for BioMedical Research (NIBR), Basel, Switzerland
Co-Authors:
Heinrich Rueeger, Rainer Machauer, Siem Jacob Veenstra, Rainer M. Lueoend, Marina Tintelnot-Blomley, Grit Laue, Karen Beltz, Barbara Vogg, Peter Schmid, Wilfried Frieauff, Derya R. Shimshek, Matthias Staufenbiel, Laura H. Jacobson
Primary Reference (PubMED ID):
26336937
Funding Source:
Not Reported
Study Goal and Principal Findings:

This study aimed at testing a novel structural class of BACE-1 inhibitor (NB-360) for pharmacokinetics, brain penetration and efficacy, in various preclinical models including the APP51/16 mouse model of AD.  The advantage to using this AD mouse model is that it more closely resembles human sporadic AD where no APP mutation is present. The data demonstrate that NB-360 is highly potent with an attractive combination of drug-like propertie. Treatment with NB-360 markedly reduced beta- amyloid pathology observed in the APP51/16 model. In addition. treatment of mice with NB-360 attenuated neuroinflammation believed to be downstream of amyloid-β accumulation. The findings indicate that reduction in amyloid-β via inhibition of BACE-1 may have the desired beneficial downstream effects on Alzheimer’s disease pathology.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
NB-360
PubMed
PubChem
ClinicalTrials
Patents
Therapeutic Target:
BACE1
Open Targets
Pharos
Agora

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Model Name:
APP51/16
PubMed
Strain/Genetic Background:
C57BL/6
Species:
Rat
Model Type:
Outbred
Model Name:
Sprague Dawley
Strain/Genetic Background:
Not Applicable
Species:
Dog
Model Type:
Non-transgenic
Model Name:
Beagle
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
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
Histopathology
beta Amyloid Deposits
Activated Astrocytes
Activated Microglia
Biochemical
Brain-beta Amyloid Peptide 38
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Amyloid Precursor Protein (APP) Metabolites
Pharmacokinetics
Drug Concentration-Plasma
Drug Concentration-Brain
Cmax
Area Under the Curve (AUC)
Tmax
Oral Bioavailability (F%)
Pharmacodynamics
Target Engagement (Reduction beta Amyloid Peptide 40-Brain)
Target Engagement (Reduction beta Amyloid Peptide 40-CSF)
Target Engagement (Reduction beta Amyloid Peptide 40-Plasma)
Biomarker
Plasma-beta Amyloid Peptide 40
CSF-beta Amyloid Peptide 40
ADME
Plasma Protein Binding
PAMPA Permeability
Share:
Print: