Transthyretin amyloid deposit (TTR amyloid deposit)

Transthyretin amyloid deposits are extracellular aggregates produced by misfolded transthyretin (TTR), a protein responsible for transporting thyroxine and retinol-binding protein. Amyloid formation occurs when dissociation and misfolding of TTR monomers lead to fibril aggregation, which accumulates in various tissues and organs. These deposits are the pathological hallmark of transthyretin amyloidosis (ATTR), which manifests in two major forms: hereditary (mutant TTR) and wild-type (senile). ATTR primarily affects the heart (causing restrictive cardiomyopathy and heart failure), peripheral/autonomic nervous systems (causing neuropathy), and other tissues. Therapeutic strategies focus on stabilizing TTR, suppressing its production, or promoting clearance/degradation of existing amyloid deposits. Drugs include TTR stabilizers (tafamidis, diflunisal, acoramidis), gene silencers (patisiran, inotersen), and monoclonal antibodies (PRX004/NNC6019-0001, ALXN2220/NI006), with novel genetic and immunotherapy approaches in development[2][3][4][5][6][7][8][9].

Other names

TTR amyloidTransthyretin amyloidATTR amyloidAmyloid transthyretin

Stabilization of TTR tetramer (preventing dissociation and amyloid formation)[2][3][8] Silencing TTR synthesis (gene silencing in liver)[3][8] Degradation and clearance of amyloid deposits via immunotherapy (monoclonal antibodies)[6] Degradation of amyloid fibrils (non-specific for some drugs; research ongoing)[8]