The University of Southampton
×
Filter your search:
University of Southampton Institutional Repository

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

Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
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.
0028-0836
254-259
Pepys, M.B.
eb147030-b7f9-448a-9d69-9adb72fe7ed2
Herbert, J.
ebd26894-ffdb-468e-9166-601f63ff3135
Huchinson, W.L.
cf757033-d268-4f95-a78c-4177fd70ca7d
Tennent, G.A.
fa3dd409-456d-46be-b9bd-dd4078f79b08
Lachmann, H.J.
d163f68f-3b39-4599-8694-8eea5e5e41cf
Gallimore, J.R.
22a402cf-e172-4690-9efc-c25cc9289db3
Lovat, L.B.
6c1c98c4-ab8b-40a2-99cc-3a4122bed28e
Bartfai, T.
9ba33919-3750-45f5-840b-0e797f11bff4
Alanine, A.
86b5130d-9fa7-4890-b2be-faed99d47ae8
Hertel, C.
9ae1332e-5167-464f-8dea-52231e0401d4
Hoffman, T.
ea1fd7d3-df7c-4e83-a7b7-de04a207f005
Jakob-Roetne, R.
38cf6c0b-f9c1-4fa9-a27e-1bf0c7a157dd
Norcross, R.D.
d53dc59e-a924-4e1d-b678-f711bd982a32
Kemp, J.A.
8ad5ae6b-e98b-4126-a816-93bb2fee4e2a
Yamamura, K.
d8fcd7b1-c07a-404b-ab52-2b73433385cb
Suzuki, M.
2834922d-0d48-40bf-a11f-72cbe1b39d08
Taylor, G.W.
9dc5c650-e163-4f33-86f3-c51f81bd22ca
Murray, S.
d24084d8-07e9-4428-9c03-49abcbb81f38
Thompson, D.
f02914bc-43d6-4944-91f6-6ee85e697788
Purvis, A.
c64e4e1c-36d7-40bf-8c1e-706a0de769c9
Kolstoe, S.
de650d4a-6146-4094-bdb0-97693e158ad3
Wood, S.P.
430faabf-7f5c-4cf6-9bcc-5955f5e09566
Hawkins, P.N.
65de4839-1ea1-47d2-a477-cc96eab8c88f
Pepys, M.B.
eb147030-b7f9-448a-9d69-9adb72fe7ed2
Herbert, J.
ebd26894-ffdb-468e-9166-601f63ff3135
Huchinson, W.L.
cf757033-d268-4f95-a78c-4177fd70ca7d
Tennent, G.A.
fa3dd409-456d-46be-b9bd-dd4078f79b08
Lachmann, H.J.
d163f68f-3b39-4599-8694-8eea5e5e41cf
Gallimore, J.R.
22a402cf-e172-4690-9efc-c25cc9289db3
Lovat, L.B.
6c1c98c4-ab8b-40a2-99cc-3a4122bed28e
Bartfai, T.
9ba33919-3750-45f5-840b-0e797f11bff4
Alanine, A.
86b5130d-9fa7-4890-b2be-faed99d47ae8
Hertel, C.
9ae1332e-5167-464f-8dea-52231e0401d4
Hoffman, T.
ea1fd7d3-df7c-4e83-a7b7-de04a207f005
Jakob-Roetne, R.
38cf6c0b-f9c1-4fa9-a27e-1bf0c7a157dd
Norcross, R.D.
d53dc59e-a924-4e1d-b678-f711bd982a32
Kemp, J.A.
8ad5ae6b-e98b-4126-a816-93bb2fee4e2a
Yamamura, K.
d8fcd7b1-c07a-404b-ab52-2b73433385cb
Suzuki, M.
2834922d-0d48-40bf-a11f-72cbe1b39d08
Taylor, G.W.
9dc5c650-e163-4f33-86f3-c51f81bd22ca
Murray, S.
d24084d8-07e9-4428-9c03-49abcbb81f38
Thompson, D.
f02914bc-43d6-4944-91f6-6ee85e697788
Purvis, A.
c64e4e1c-36d7-40bf-8c1e-706a0de769c9
Kolstoe, S.
de650d4a-6146-4094-bdb0-97693e158ad3
Wood, S.P.
430faabf-7f5c-4cf6-9bcc-5955f5e09566
Hawkins, P.N.
65de4839-1ea1-47d2-a477-cc96eab8c88f

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).

Record type: Article

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.

Text
sap_cphpc.(3)pdf.pdf - Version of Record
Restricted to Registered users only
Download (382kB)

More information

Published date: 16 May 2002
Related URLs:
Learn more about Biological Sciences research

Identifiers

Local EPrints ID: 35611
URI: http://eprints.soton.ac.uk/id/eprint/35611
DOI: doi:10.1038/417254a
ISSN: 0028-0836
PURE UUID: ca541a16-0728-48b7-9790-567b182186af

Catalogue record

Date deposited: 22 May 2006
Last modified: 15 Mar 2024 07:53

Export record

Altmetrics

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

Download statistics

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

Library staff additional information
Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×