Antibodies to human serum amyloid P component eliminate visceral amyloid deposits

Research output: Contribution to journalArticle

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Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. / Bodin, K; Ellmerich, S; Kahan, MC; Tennent, GA; Loesch, A; Gilbertson, JA; Hutchinson, WL; Mangione, PP; Gallimore, JR; Millar, DJ; Minogue, S; Dhillon, AP; Taylor, GW; Bradwell, Arthur; Petrie, A; Gillmore, JD; Bellotti, V; Botto, M; Hawkins, PN; Pepys, MB.

In: Nature, Vol. 468, No. 7320, 01.11.2010, p. 93-97.

Research output: Contribution to journalArticle

Harvard

Bodin, K, Ellmerich, S, Kahan, MC, Tennent, GA, Loesch, A, Gilbertson, JA, Hutchinson, WL, Mangione, PP, Gallimore, JR, Millar, DJ, Minogue, S, Dhillon, AP, Taylor, GW, Bradwell, A, Petrie, A, Gillmore, JD, Bellotti, V, Botto, M, Hawkins, PN & Pepys, MB 2010, 'Antibodies to human serum amyloid P component eliminate visceral amyloid deposits', Nature, vol. 468, no. 7320, pp. 93-97. https://doi.org/10.1038/nature09494

APA

Bodin, K., Ellmerich, S., Kahan, MC., Tennent, GA., Loesch, A., Gilbertson, JA., Hutchinson, WL., Mangione, PP., Gallimore, JR., Millar, DJ., Minogue, S., Dhillon, AP., Taylor, GW., Bradwell, A., Petrie, A., Gillmore, JD., Bellotti, V., Botto, M., Hawkins, PN., & Pepys, MB. (2010). Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature, 468(7320), 93-97. https://doi.org/10.1038/nature09494

Vancouver

Bodin K, Ellmerich S, Kahan MC, Tennent GA, Loesch A, Gilbertson JA et al. Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature. 2010 Nov 1;468(7320):93-97. https://doi.org/10.1038/nature09494

Author

Bodin, K ; Ellmerich, S ; Kahan, MC ; Tennent, GA ; Loesch, A ; Gilbertson, JA ; Hutchinson, WL ; Mangione, PP ; Gallimore, JR ; Millar, DJ ; Minogue, S ; Dhillon, AP ; Taylor, GW ; Bradwell, Arthur ; Petrie, A ; Gillmore, JD ; Bellotti, V ; Botto, M ; Hawkins, PN ; Pepys, MB. / Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. In: Nature. 2010 ; Vol. 468, No. 7320. pp. 93-97.

Bibtex

@article{110db9cc56d743198a2819d489705fff,
title = "Antibodies to human serum amyloid P component eliminate visceral amyloid deposits",
abstract = "Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries(1). Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present(1). There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation(1). Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous(1). There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP)(2,3). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-D-proline compound CPHPC4, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.",
author = "K Bodin and S Ellmerich and MC Kahan and GA Tennent and A Loesch and JA Gilbertson and WL Hutchinson and PP Mangione and JR Gallimore and DJ Millar and S Minogue and AP Dhillon and GW Taylor and Arthur Bradwell and A Petrie and JD Gillmore and V Bellotti and M Botto and PN Hawkins and MB Pepys",
year = "2010",
month = nov
day = "1",
doi = "10.1038/nature09494",
language = "English",
volume = "468",
pages = "93--97",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7320",

}

RIS

TY - JOUR

T1 - Antibodies to human serum amyloid P component eliminate visceral amyloid deposits

AU - Bodin, K

AU - Ellmerich, S

AU - Kahan, MC

AU - Tennent, GA

AU - Loesch, A

AU - Gilbertson, JA

AU - Hutchinson, WL

AU - Mangione, PP

AU - Gallimore, JR

AU - Millar, DJ

AU - Minogue, S

AU - Dhillon, AP

AU - Taylor, GW

AU - Bradwell, Arthur

AU - Petrie, A

AU - Gillmore, JD

AU - Bellotti, V

AU - Botto, M

AU - Hawkins, PN

AU - Pepys, MB

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries(1). Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present(1). There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation(1). Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous(1). There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP)(2,3). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-D-proline compound CPHPC4, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.

AB - Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries(1). Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present(1). There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation(1). Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous(1). There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP)(2,3). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-D-proline compound CPHPC4, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.

U2 - 10.1038/nature09494

DO - 10.1038/nature09494

M3 - Article

VL - 468

SP - 93

EP - 97

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7320

ER -