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

Record type: Article

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.

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Citation

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).

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Published date: 16 May 2002

Identifiers

Local EPrints ID: 35611
URI: http://eprints.soton.ac.uk/id/eprint/35611
ISSN: 0028-0836
PURE UUID: ca541a16-0728-48b7-9790-567b182186af

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Date deposited: 22 May 2006
Last modified: 17 Jul 2017 15:47

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Contributors

Author: M.B. Pepys
Author: J. Herbert
Author: W.L. Huchinson
Author: G.A. Tennent
Author: H.J. Lachmann
Author: J.R. Gallimore
Author: L.B. Lovat
Author: T. Bartfai
Author: A. Alanine
Author: C. Hertel
Author: T. Hoffman
Author: R. Jakob-Roetne
Author: R.D. Norcross
Author: J.A. Kemp
Author: K. Yamamura
Author: M. Suzuki
Author: G.W. Taylor
Author: S. Murray
Author: D. Thompson
Author: A. Purvis
Author: S. Kolstoe
Author: S.P. Wood
Author: P.N. Hawkins

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