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Review
. 2024 Jun 23;16(6):e62981.
doi: 10.7759/cureus.62981. eCollection 2024 Jun.

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

Prashil Dave  1 , Puneet Anand  2 , Azra Kothawala  3 , Prakhyath Srikaram  4 , Dipsa Shastri  5 , Anwar Uddin  1 , Jill Bhavsar  6 , Andrew Winer  7
Affiliations
Review

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

Prashil Dave et al. Cureus. .

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.

Keywords: amyloid transthyretin; amyloidosis treatment; hereditary transthyretin amyloidosis; management of hereditary amyloidosis; rna interference therapeutic; transthyretin amyloidosis.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

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