Treatment of Cardiac Amyloidosis—Disease Modifying Therapies in ATTR: Pharmacological Point of View

Transthyretin amyloidosis (ATTR amyloidosis) is a progressive disease, ATTR amyloidosis can be treated specifically in three different mechanisms. The first mechanism stops of amyloidogenic TTR synthesis through various methods. Inotersen and Eplontersen are antisense oligonucleotide, which “silence” or block TTR protein synthesis, results in a decrease in TTR expression. Patisiran and Vutrisiran are RNA interference therapies targeting the gene encoding transthyretin (TTR) resulting in reduction the amount of mutant transthyretin that is synthesized by the liver. Clustered regularly interspaced short palindromic repeats (CRISPR or CRISPR-associated protein 9 (CRISPR Cas9) is technology of a gene editing that enable to modifies the genome sequence by produce base substitutions, insertion, or deletions in the genome. The second mechanism include medication that stabilized the TTR tetramer by binding to the T4-binding site on the TTR to prevent misfolding and deposition of monomers and oligomers. In phase III clinical trials, Tafamidis and Acoramidis have been shown to reduce cardiovascular-related hospitalizations. TTR stabilizers and silencers can prevent disease deterioration but do not improve advanced staged of ATTR CMs. Indeed, the third newly mechanism enhance protein misfolding removal. NI301A and PRX004 bind to specific epitope, located in misfolding monomers and oligomers but unexposed in TTR’s naturally folded conformation, this enhance amyloid deposit removal through phagocytic cells specific monoclonal antibodies that directly enhance the clearance of toxic amyloid by stimulating their removal through phagocytic cells to improve organ function.