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, pp. 254-259. (doi:10.1038/417254a).

Download

[img] PDF sap_cphpc.(3)pdf.pdf - Version of Record
Restricted to Registered users only

Download (382kB)

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
Digital Object Identifier (DOI): doi:10.1038/417254a
ISSNs: 0028-0836 (print)
Related URLs:
Subjects:
ePrint ID: 35611
Date :
Date Event
16 May 2002Published
Date Deposited: 22 May 2006
Last Modified: 16 Apr 2017 22:08
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/35611

Actions (login required)

View Item View Item