Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis.
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.
Gillmore
Julian D
JD
Centre for Amyloidosis and Acute Phase Proteins and the National Amyloidosis Centre, University College London Medical School, London, UK.
Tennent
Glenys A
GA
Hutchinson
Winston L
WL
Gallimore
Janet Ruth
JR
Lachmann
Helen J
HJ
Goodman
Hugh J B
HJ
Offer
Mark
M
Millar
David J
DJ
Petrie
Aviva
A
Hawkins
Philip N
PN
Pepys
Mark B
MB
D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D002264:Carboxylic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D000683:Serum Amyloid P-Component / Q000187:drug effects* / Q000378:metabolism*
D002264:Carboxylic Acids; D000683:Serum Amyloid P-Component