Which treatments for AA (inflammatory) amyloidosis are currently being investigated?

Updated: Jan 08, 2021
  • Author: Jefferson R Roberts, MD; Chief Editor: Herbert S Diamond, MD  more...
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New approaches to the treatment of AA amyloidosis that are currently undergoing clinical trials.

A low–molecular-weight sulfonated molecule has been developed that interferes with fibril formation and deposition of amyloid by inhibiting interaction of SAA with glycosaminoglycans. In experimentally induced murine AA amyloidosis, this drug (NC-503) has been shown to reduce the amount of amyloid deposits.

Dimerization of human SAP molecules in vivo with a palindromic compound (CPHPC) triggers very rapid clearance of the complexed protein by the liver, depleting SAP from the circulation within a few hours of drug administration.

The plasma glycoprotein serum amyloid P component (SAP) is a universal constituent of all types of amyloid plaques, and potentiates the amyloidogenic process. A study by Bodin and colleagues tested a two-step therapeutic strategy for amyloidosis that targeted SAP by first pharmacologically depleting circulating levels of SAP with the bivalent crosslinker CPHPC, and then subsequently administering anti-human-SAP antibodies. In mice transgenic for human SAP, an experimental model of systemic AA amyloidosis, this treatment regimen produced almost complete regression of hepatic and splenic amyloid deposits 4 weeks after anti-SAP treatment. [39] In a phase I trial in 15 patients, this treatment safely triggered clearance of amyloid deposits from the liver and some other tissues. [40]

Interactions between heparan-sulfate and dermatan-sulfate glycosaminoglycan (GAG)-containing proteoglycans and the misfolded amyloid precursor protein are also considered important for amyloidogenesis and the stabilization of amyloid. This insight has been used in a clinical trial to destabilize amyloid deposits with eprodisate, a negatively charged, sulfonated GAG analog, which binds to GAG-binding sites of the amyloid fibrils. [41]  However, in the phase III trial, eprodisate did not meet the primary endpoint in slowing renal function decline. [42]

A study demonstrated the efficacy of pegylated INF-alpha once a week in FMF in the induction of a durable disease remission and the almost complete reversal of secondary renal AA amyloidosis. [43]

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