Transthyretin (TTR) amyloidosis, also known as transthyretin-related familial amyloidotic polyneuropathy (ATTR-FAP), is a fatal hereditary systemic amyloidosis caused by mutant forms of TTR. Although conventional treatments for ATTR-FAP, such as liver transplantation (LT) and TTR tetramer stabilizer, reportedly halt the progression of clinical manifestation, these therapies have several limitations. Oligonucleotide-based therapy, e.g. small interfering RNA (siRNA)- and antisense oligonucleotides (ASOs)-based therapy, hold enormous potential for the treatment of intractable diseases such as ATTR-FAP, by specifically regulating the gene responsible for the disease. Clinical evidence strongly suggests that LT inhibits mutant TTR production, thus improving the manifestation of ATTR-FAP. Therefore, an oligonucleotide-based therapy for ATTR-FAP, which reduces the production of TTR by the liver, has recently been developed in preclinical and clinical studies. This review focuses on recent advances in oligonucleotide-based therapy and future prospects of next-generation oligonucleotide-based drugs for therapeutic use against ATTR-FAP.
Keywords: amyloidosis; antisense oligonucleotide; gene silencing; genome editing; small interfering RNA; transthyretin.