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Updated: Apr 6, 2026

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis
Abstract:
The amyloid deposits that cause disease in systemic amyloidosis always contain the normal plasma protein, serum amyloid P (SAP) component. SAP is the target of a novel immunotherapy approach now being developed to eliminate amyloid deposits. The treatment is enabled by, and critically depends on, the use of the drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, GSK2315698, Ro 63-8695), which depletes circulating SAP almost completely but leaves some SAP in amyloid deposits for specific recognition by subsequently administered therapeutic anti-SAP antibodies. Herein, we report a mechanistic model that predicts, with clinically acceptable precision, the exposure-response relationship for CPHPC, both in healthy individuals and in patients with systemic amyloidosis. The model covariates are gender, renal function, total amyloid load, and presence of hepatic amyloid, all of which are known at baseline. The model is being used to predict individualized dosing regimens in an ongoing, first-in-human study with anti-SAP antibodies.
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