| Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis. | |
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MedLine Citation:
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PMID: 20064157 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Serum amyloid P component (SAP) is a universal constituent of amyloid deposits and contributes to their formation and/or persistence. We therefore developed CPHPC ((R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexa-noyl]pyrrolidine-2 carboxylic acid), a novel bis(D-proline) drug, to specifically target SAP and report here a first, exploratory, open label proof of principle study in systemic amyloidosis. CPHPC produced sustained, >95% depletion of circulating SAP in all patients and c. 90% reduction in the SAP content of the two amyloidotic organs that became available. There were no significant adverse effects of either SAP depletion or CPHPC itself. No accumulation of amyloid was demonstrable by SAP scintigraphy in any patient on the drug. In hereditary fibrinogen amyloidosis, which is inexorably progressive, proteinuria was reduced in four of five patients receiving CPHPC and renal survival was prolonged compared to a historical control group. These promising clinical observations merit further study. |
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Authors:
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Julian D Gillmore; Glenys A Tennent; Winston L Hutchinson; Janet Ruth Gallimore; Helen J Lachmann; Hugh J B Goodman; Mark Offer; David J Millar; Aviva Petrie; Philip N Hawkins; Mark B Pepys |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-08 |
Journal Detail:
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Title: British journal of haematology Volume: 148 ISSN: 1365-2141 ISO Abbreviation: Br. J. Haematol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-05-04 Completed Date: 2010-06-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 760-7 Citation Subset: IM |
Affiliation:
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Centre for Amyloidosis and Acute Phase Proteins and the National Amyloidosis Centre, University College London Medical School, London, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Amyloidosis / blood, drug therapy*, metabolism* Carboxylic Acids / chemistry, metabolism, pharmacology, therapeutic use* Female Humans Male Middle Aged Proteinuria / drug therapy Serum Amyloid P-Component / drug effects*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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G97900510//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Carboxylic Acids; 0/Serum Amyloid P-Component |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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