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Updated: Jul 12, 2025
06:27
Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
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Fibrin-Targeting Immunotherapy for Dementia.
A B Kantor1, K Akassoglou, J B Stavenhagen
1Jeffrey Stavenhagen, PhD, Therini Bio, Inc, Sacramento, CA, USA,
The Journal of Prevention of Alzheimer'S Disease
|October 24, 2023
Summary
Blood-brain barrier disruption allows fibrinogen to enter the brain, triggering inflammation and neurodegeneration. Targeting the fibrin P2 epitope with antibodies like THN391 shows promise for treating Alzheimer's disease and other neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Blood-brain barrier (BBB) disruption is an early event in Alzheimer's disease pathogenesis.
- Leaked fibrinogen converts to fibrin, exposing a P2 epitope that activates innate immune cells and causes neuroinflammation.
- This fibrin-mediated inflammation is toxic to neurons and implicated in neurodegenerative diseases.
Purpose of the Study:
- To investigate the role of fibrin P2 epitope in neuroinflammation and neurodegeneration.
- To evaluate the therapeutic potential of targeting the fibrin P2 epitope with monoclonal antibodies.
Main Methods:
- Utilized mouse monoclonal antibody 5B8 targeting the fibrin P2 epitope.
- Assessed the efficacy of 5B8 in reducing neurodegeneration and neuroinflammation in animal models.
- Developed THN391, a humanized antibody with enhanced affinity for fibrin P2.
Main Results:
- Antibody 5B8 demonstrated reduced neurodegeneration and neuroinflammation in Alzheimer's and multiple sclerosis models.
- THN391 exhibits 100-fold higher affinity for fibrin P2 and improved properties over 5B8.
- THN391 is currently undergoing Phase 1 clinical trials.
Conclusions:
- Targeting the fibrin P2 epitope is a viable therapeutic strategy for neurodegenerative diseases.
- Monoclonal antibodies like THN391 offer a promising approach for treating conditions associated with BBB disruption and neuroinflammation.
- Further clinical investigation of THN391 is warranted.
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