Specific Therapy in Transthyretin Amyloid Cardiomyopathy: Future Perspectives Beyond Tafamidis

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a relatively prevalent cause of morbidity and mortality. Over the recent years, development of disease-modifying treatments has enabled stabilization of the circulating transthyretin tetramer and suppression of its hepatic production, resulting in a remarkable improvement in survival of patients with ATTR-CM. Second-generation drugs for silencing are currently under investigation in randomized clinical trials. In vivo gene editing of transthyretin has been achieving unanticipated suppression of hepatic production in ATTR-CM. Trials of antibodies inducing the active removal of transthyretin amyloid deposits in the heart are ongoing, and evidence has gathered for exceptional spontaneous regression of ATTR-CM.

Keywords: Amyloidogenic cascade; Antibody-mediated amyloid removal; Antisense oligonucleotide (ASO); Disease-modifying treatments; Small interfering RNAs (siRNA); Transthyretin amyloidosis.