Serum amyloid P-component (SAP) (SAP)

Serum amyloid P-component (SAP) is a 25 kDa pentameric glycoprotein and a member of the pentraxin family, produced exclusively by the liver and secreted into the blood [5, 9]. It is a universal, non-fibrillar constituent of all human amyloid deposits, where it binds to amyloid fibrils in a calcium-dependent manner, protecting them from proteolytic degradation and promoting their persistence [5, 10]. In addition to its role in amyloidosis, SAP functions as a soluble pattern recognition receptor in the innate immune system, binding to DNA, chromatin, and various pathogens to facilitate their clearance [3, 9]. Therapeutic strategies targeting SAP include the use of small molecules like miridesap (CPHPC) to deplete circulating SAP levels by inducing rapid hepatic clearance, thereby destabilizing tissue amyloid deposits [1, 6]. Other approaches involve monoclonal antibodies like dezamizumab to trigger immune-mediated removal of amyloid or the use of recombinant SAP (PRM-151) to treat fibrotic diseases by modulating monocyte differentiation [13, 17]. SAP is also being investigated as a potential target in neurodegenerative disorders such as Alzheimer's disease and Lewy body dementia due to its neurotoxic effects and association with amyloid plaques [5, 8].

Other names

Amyloid P componentAPCSPTX2Pentraxin 2HEL-S-92n9.5S alpha-1-glycoprotein

Drugs targeting SAP utilize several distinct mechanisms: Miridesap (CPHPC) acts as a palindromic cross-linker that dimerizes SAP molecules, triggering their rapid clearance by the liver and depleting circulating and tissue-bound SAP [1, 4]. Dezamizumab is a monoclonal antibody that targets SAP remaining in amyloid deposits after plasma depletion, facilitating immune-mediated clearance of the fibrils [17]. PRM-151 is a recombinant form of SAP that acts as an agonist to inhibit the differentiation of monocytes into profibrotic fibrocytes and promote anti-inflammatory macrophage phenotypes [13].