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 per thousand deaths in developed countries1. Localised amyloid can also be very serious, 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 present1. There is therefore a major unmet medical need for therapy which 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 protein can arrest amyloid accumulation1. Unfortunately control of fibril protein production is not possible in some forms of amyloidosis and in others is often slow and hazardous1. 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 which 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.

Leukocyte Cell–Derived Chemotaxin 2–Associated Amyloidosis

“…SAP is a major component of amyloid deposits of any type. Antibodies to human SAP were shown to eliminate visceral AA deposits in mice (57). It is critical not to misdiagnose ALECT2 amyloidosis as AL amyloidosis to avoid harmful therapy (20).…”

Serum amyloid P component facilitates DNA clearance and inhibits plasmid transfection: implications for human DNA vaccine

“…The safety of SAP depletion by CHPHC administration has been recently confirmed in a clinical investigation. 48 We therefore suggest that SAP suppression by chemicals, such as CHPHC, might be a novel direction to enhance the efficiency of DNA immunization in human beings. We also suggest that some special nanomaterials that can prevent DNA vaccines from hSAP binding may be a potential novel adjuvant for human DNA vaccines.…”

Amyloidosis

“…87 The Royal Free group in London recently demonstrated that CPHPC followed by anti-SAP antibodies resulted in a quick removal of almost all AA amyloid from the tissues in mice with AA amyloidosis. 88 If this dramatic effect on amyloid can be replicated in humans, it may lead to a major change in the prognosis for patients with all types of systemic amyloidosis.…”