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Updated: Jun 14, 2026

Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease
Published on: May 13, 2010
Drug targets for amyloidosis
Simon E Kolstoe1, Steve P Wood
1Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, University College London, Rowland Hill Street, London NW3 2PF, UK.
Researchers explored novel strategies for treating systemic amyloidoses, including Alzheimer's disease. A bivalent drug, CPHPC, effectively clears serum amyloid P component, promoting natural amyloid clearance mechanisms with potential CNS applications.
Area of Science:
- Biochemistry
- Neuroscience
- Pharmacology
Background:
- The amyloid hypothesis links protein misfolding to neurodegenerative disorders.
- Current Alzheimer's disease (AD) treatments targeting amyloid beta-peptide (Abeta) have shown limited success in human trials.
- Systemic amyloidoses share features with central nervous system (CNS) disorders, suggesting transferable therapeutic strategies.
Purpose of the Study:
- To investigate small molecule approaches for treating systemic amyloidoses.
- To develop compounds that stabilize transthyretin (TTR) or promote amyloid clearance.
- To explore targeting serum amyloid P component (SAP) for a more generalized amyloid removal strategy.
Main Methods:
- Development of small molecules to stabilize TTR, preventing structural transition or promoting clearance.
- Design and application of a bivalent drug, CPHPC, to cross-link pentameric SAP molecules.
- Assessment of SAP clearance from circulation following CPHPC administration.
Main Results:
- Effective TTR stabilizer compounds binding to thyroxine-binding sites were developed.
- CPHPC demonstrated rapid elimination of SAP from circulation by cross-linking pentamers.
- The SAP targeting strategy shows potential for application in CNS disorders.
Conclusions:
- Targeting SAP with bivalent molecules like CPHPC offers a promising therapeutic strategy for systemic amyloidoses.
- This approach leverages natural clearance mechanisms and may extend to neurodegenerative diseases.
- Further research is warranted to explore the full therapeutic potential of SAP targeting in CNS conditions.
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