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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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 |
| Item ID: | 35611 |
| Date Deposited: | 22 May 2006 |
| Last Modified: | 28 Jun 2012 10:21 |
| Contributors: | Pepys, M.B. (Author) Herbert, J. (Author) Huchinson, W.L. (Author) Tennent, G.A. (Author) Lachmann, H.J. (Author) Gallimore, J.R. (Author) Lovat, L.B. (Author) Bartfai, T. (Author) Alanine, A. (Author) Hertel, C. (Author) Hoffman, T. (Author) Jakob-Roetne, R. (Author) Norcross, R.D. (Author) Kemp, J.A. (Author) Yamamura, K. (Author) Suzuki, M. (Author) Taylor, G.W. (Author) Murray, S. (Author) Thompson, D. (Author) Purvis, A. (Author) Kolstoe, S. (Author) Wood, S.P. (Author) Hawkins, P.N. (Author) |
| Date: | 16 May 2002 |
| Status: | Published |
| Contact Email Address: | m.pepys@rfc.ucl.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/35611 |
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