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).

Download

[img] PDF - Publishers print
Restricted to Registered users only

Download (373Kb)
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
URI: http://eprints.soton.ac.uk/id/eprint/35611

Actions (login required)

View Item View Item

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics