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Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis.

Abstract
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.
AuthorsJulian 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
JournalBritish journal of haematology (Br J Haematol) Vol. 148 Issue 5 Pg. 760-7 (Mar 2010) ISSN: 1365-2141 [Electronic] England
PMID20064157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carboxylic Acids
  • Serum Amyloid P-Component
Topics
  • 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)

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