RNA Interference Therapeutics for Hereditary Amyloidosis: A Narrative Review of Clinical Trial Outcomes and Future Directions

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2024 Jul 24

PMID 39044869

Authors

Prashil Dave

Puneet Anand

Azra Kothawala

Prakhyath Srikaram

Dipsa Shastri

Anwar Uddin

Jill Bhavsar

Andrew Winer

Affiliations

Soon will be listed here.

Abstract

Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant, life-threatening genetic disorder caused by a single-nucleotide variant in the transthyretin gene. This mutation leads to the misfolding and deposition of amyloid in various body organs. Both mutant and wild-type transthyretin contribute to the resulting polyneuropathy and cardiomyopathy, leading to significant sensorimotor disturbances and severe cardiac conditions such as heart failure and arrhythmias, thereby impacting quality of life. Despite several treatments, including orthotopic liver transplantation and transthyretin tetramer stabilizers, their limitations persisted until the introduction of RNA interference (RNAi). RNAi, a means to regulate mRNA stability and translation of targeted genes, has brought about significant changes in treatment strategies for ATTR with the introduction of patisiran in 2018. This study reviews patisiran, vutrisiran, inotersen, and eplontersen, developed for the treatment of ATTR. It provides an overview of the clinical trial outcomes, focusing mainly on quality of life, adverse reactions, and the future of RNAi-based therapies.

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