Transthyretin-Related Amyloidosis Medication

Updated: May 01, 2020
  • Author: Jefferson R Roberts, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Medication Summary

Despite recent drug approvals, liver transplantation remains the gold standard for treating transthyretin-related amyloidosis (ATTR). Multi-organ transplantation (heart, liver and kidney) has been successful in slowing the natural course of the disease. In 2018, the US Food and Drug Administration (FDA) approved patisiran and inotersen for treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adults. [35, 37] In Europe, tafamidis is approved for stage I FAP. Research continues to identify and refine effective medical treatments for preventing the deposition of amyloid fibrils.

Cautious, closely monitored medical treatment for ATTR cardiomyopathy and consideration of implantable cardioverter-defibrillator (ICD) placement are required, as the restrictive pathophysiology of the heart failure differs from the more common hypertrophic or dilated varieties and standard treatments such as beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or diuretics could worsen symptoms. Digoxin can increase local amyloid fibril levels in the heart [22]


siRNA Agents

Class Summary

Anti-transthyretin small interfering ribonucleic acid (siRNA) agents causes degradation of mutant and wild-type TTR mRNA through RNA interference.

Patisiran (Onpattro)

Patisiran is an siRNA agent that reduces serum transthyretin (TTR) protein and TTR protein deposits in tissues. It is indicated for treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults.


Antisense Oligonucleotides

Class Summary

In a clinical trial, inotersen, an antisense oligonucleotide, has improved neurological scores compared with placebo. [37]

Inotersen (Tegsedi)

Inotersen is an antisense oligonucleotide that causes degradation of mutant and wild-type transthyretin mRNA by binding TTR mRNA. This action results in reduced TTR protein in serum and tissue. It is indicated for polyneuropathy of hATTR in adults.