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The neuroprotective effects of cerebrolysin in a transgenic model of Alzheimer's disease are associated with improved behavioral performance

Bibliographic

Year of Publication:
2003
Contact PI Name:
Eliezer Masliah
Contact PI Affiliation:
Department of Neurosciences, University of California, San Diego, La Jolla, California, USA
Co-Authors:
E. Rockenstein, A. Adame, M. Mante, H. Moessler, M. Windisch
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
EBEWE Pharmaceuticals
Study Goal and Principal Findings:

Cerebrolysin is a peptide mixture with neurotrophic effects that might have the ability of both reducing amyloid burden and improving synaptic plasticity in Alzheimer's disease (AD). In order to determine if Cerebrolysin is capable of ameliorating the neurodegenerative and behavioral alterations associated with amyloid beta (A beta) production; transgenic (tg) mice expressing mutant human amyloid precursor protein (APP) under the Thy1 promoter were treated with Cerebrolysin or saline alone starting at 3 or 6 months of age for a total of three months. Animals were then tested behaviorally (at 6 and 9 months of age respectively) in the water maze and then analyzed neuropathologically for amyloid burden, synaptic density, astrogliosis and apoptosis. Performance analysis in the water maze showed that in the younger tg mice cohort, Cerebrolysin treatment significantly ameliorated the performance deficits. In the older cohort, there was a trend toward improved performance in the learning curve. Neuropathological examination showed that in both age/treatment groups, Cerebrolysin promoted synaptic regeneration, and reduced the proportion of neurons displaying DNA fragmentation by the (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) method. Moreover, Cerebrolysin treatment reduced A beta burden by 43% in the young group and by 27% in the older group. Taken together, these results suggest that Cerebrolysin treatment might have beneficial effects in patients with cognitive impairment by reducing A beta accumulation and promoting the preservation of synaptic terminals.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Peptide
Therapeutic Agent:
Cerebrolysin
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
APP
Strain/Genetic Background:
C57BL/6XSwiss Webster F1

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
Morris Water Maze
Histopathology
beta Amyloid Deposits
beta Amyloid Load
Neurodegeneration
Activated Astrocytes
Immunochemistry
Apoptosis
Synaptophysin
Glial Fibrillary Acidic Protein (GFAP)
Brain-beta Amyloid Deposits