Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
Top Cited Papers
- 16 May 2002
- journal article
- research article
- Published by Springer Nature in Nature
- Vol. 417 (6886) , 254-259
- https://doi.org/10.1038/417254a
Abstract
The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes.Keywords
This publication has 33 references indexed in Scilit:
- Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A proteinThe Lancet, 2001
- Curative hepatorenal transplantation in systemic amyloidosis caused by the Glu526Val fibrinogen α‐chain variant in an English familyQJM: An International Journal of Medicine, 2000
- AMYLOIDOSIS: A REVIEW OF RECENT DIAGNOSTIC AND THERAPEUTIC DEVELOPMENTSBritish Journal of Haematology, 1997
- Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component geneNature Medicine, 1997
- Crystal structure of a decameric complex of human serum amyloid P component with bound dAMPJournal of Molecular Biology, 1997
- Amyloid P component. A critical reviewAmyloid, 1997
- Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis.Proceedings of the National Academy of Sciences, 1995
- Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure.Proceedings of the National Academy of Sciences, 1994
- Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosisThe Lancet, 1993
- SPECIFIC CHEMICAL DISSOCIATION OF FIBRILLAR AND NON-FIBRILLAR COMPONENTS OF AMYLOID DEPOSITSThe Lancet, 1984