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


Pepys, M.B., Herbert, J., Huchinson, W.L., Tennent, G.A., Lachmann, H.J., Gallimore, J.R., Lovat, L.B., Bartfai, T., Alanine, A., Hertel, C., Hoffman, T., Jakob-Roetne, R., Norcross, R.D., Kemp, J.A., Yamamura, K., Suzuki, M., Taylor, G.W., Murray, S., Thompson, D., Purvis, A., Kolstoe, S., Wood, S.P. and Hawkins, P.N. (2002) Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature, 417, 254-259. (doi:10.1038/417254a).

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Original Publication URL: http://dx.doi.org/10.1038/417254a

Description/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.

Item Type: Article
ISSNs: 0028-0836 (print)
Related URLs:
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 35611
Date Deposited: 22 May 2006
Last Modified: 27 Mar 2014 18:22
Contact Email Address: m.pepys@rfc.ucl.ac.uk
URI: http://eprints.soton.ac.uk/id/eprint/35611

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