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Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis

Pepys, MB; Herbert, J; Hutchinson, WL; Tennent, GA; Lachmann, HJ; Gallimore, JR; Lovat, LB; ... Hawkins, PN; + view all (2002) Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. NATURE , 417 (6886) 254 - 259. 10.1038/417254a.

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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.

Type: Article
Title: Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
DOI: 10.1038/417254a
Keywords: SYSTEMIC AMYLOIDOSIS, ALZHEIMER-DISEASE, LIVER-TRANSPLANTATION, AA AMYLOIDOSIS, IN-VIVO, X-RAY, MOUSE, DEPOSITS, PROGRAM, PROTEIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: http://discovery.ucl.ac.uk/id/eprint/153051
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