Systemic amyloid fibrils

Systemic amyloid fibrils are insoluble, misfolded protein aggregates that deposit in the extracellular space of various organs, leading to progressive organ dysfunction and death (Merlini & Bellotti, 2003). These fibrils are characterized by a cross-beta sheet structure and are formed from various precursor proteins, such as immunoglobulin light chains (AL), transthyretin (ATTR), or serum amyloid A (AA) (Sipe et al., 2016). In systemic amyloidosis, the accumulation of these fibrils disrupts the normal architecture and function of the heart, kidneys, liver, and peripheral nerves (Gertz et al., 2016). Therapeutic strategies targeting the fibrils themselves involve monoclonal antibodies, such as birtamimab and anselamimab, designed to bind specifically to the misfolded conformation, triggering immune-mediated clearance by macrophages (Edwards et al., 2017). This approach aims to reduce the existing amyloid burden and restore organ function, complementing upstream therapies that inhibit the production or stabilization of precursor proteins (Benson et al., 2018).

Other names

Amyloid depositsAmyloid aggregatesInsoluble protein fibrilsAmyloid plaquesPathological protein aggregates

Monoclonal antibody-mediated clearance of amyloid deposits via antibody-dependent cellular phagocytosis (ADCP) and neutralization of proteotoxic species (Edwards et al., 2017).