How does eplontersen work (its mechanism of action)?
Eplontersen is an antisense oligonucleotide designed to reduce production of the mutant protein that drives transthyretin (TTR) amyloidosis. It targets TTR messenger RNA (mRNA) in the liver and promotes its degradation, which lowers circulating TTR levels and reduces the amount of TTR available to form amyloid deposits [1].
What does eplontersen target in the body?
Eplontersen binds to specific sequences on TTR mRNA, leading to reduced TTR protein synthesis. Because most circulating TTR is produced in the liver, the liver is the key tissue where lowering TTR production occurs [1].
What changes downstream in disease biology?
By decreasing TTR protein in the bloodstream, eplontersen aims to slow or prevent the formation of new amyloid deposits and reduce the ongoing amyloid burden that damages nerves and organs in TTR amyloidosis [1].
Why does lowering TTR matter in transthyretin amyloidosis?
In TTR amyloidosis, misfolding and aggregation of TTR proteins form amyloid fibrils. Lowering TTR reduces the supply of the protein that can misfold and deposit, which is the core therapeutic strategy behind eplontersen [1].
What you should know about the drug class (antisense oligonucleotide)
Like other antisense therapies, eplontersen acts at the RNA level rather than directly blocking a receptor or enzyme. Its effect comes from binding to target mRNA and reducing translation of the disease-relevant protein [1].
Sources
[1] https://www.accessdata.fda.gov/drugsatfda_docs/label/