Neuro · Vol. 11, No. 1 · 2025 · pp. 5–8 · e-ISSN 2377-1607

New Treatments for Amyloidosis Neuropathy

Yung-Chih Cheng, PhD

Department of Cell Biology, Boston Children’s Hospital, Q-State Bioscience, MA 02139, USAUnited States

DOI: https://doi.org/10.17140/noj.2025.v11.i01.pp05-08.1847 · Published 2025-04-20 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2025 The Author(s)

Also available as PDF (figures and tables appear in the PDF).

Abstract

Peripheral neuropathy is a type of neurological disorder in which patients with complex inherited neurological defects present significant phenotype in the peripheral nervous system. Hereditary amyloidogenic transthyretin (hATTR) neuropathy is typical polyneuropathy caused by single-nucleotide variants in the gene encoding transthyretin (TTR) and leads to transthyretin misfolding and systemic deposition of amyloid. One of the clinical hallmarks of hATTR neuropathy is polyneuropathy of the destruction of the somatic and autonomic peripheral nervous system, leading to loss of autonomy. Progressive amyloid accumulation also causes multi-organ dysfunction and death. There are many therapeutics that have been proposed and developed in these years. These therapies aim to reduce or eliminate hATTR from the plasma, stabilize the hATTR to prevent deposition, and dissolute the amyloid misfolding matrix. Recently, gene therapy strategy is being deployed to treat recessive genetic disorders by eliminating the expression of the mutated genes. Thus, gene-silencing approaches have been used to manage this amyloidosis neuropathy in the broad stages and produce some degree of improvement of this disease. Food and Drug Administration (FDA) approved Inotersen (an antisense oligonucleotide (ASO)) and patisiran (a small interfering ribonucleic acid (siRNA) for the treatment of hATTR polyneuropathy to suppress hATTR expression. Inotersen, a 2’-O-methoxyethylmodified ASO, which acts by reducing the production of transthyretin, and has been demonstrated to improve the quality of life in early hereditary transthyretin amyloidosis polyneuropathy. I here focus on the RNA-targeted therapy with particular emphasis on the molecular mechanisms by which antisense oligonucleotide can be designed to modulate transthyretin RNA function for being a novel therapy for hereditary amyloidosis neuropathy

Keywords: Peripheral neuropathy; Amyloidosis; Antisense oligonucleotide (ASO); Peripheral neuropathy; Amyloidosis; Antisense oligonucleotide (ASO)

Conclusion

Currently, there have been a couple of treatment options for hAT-

TR patients. Primarily, RNA therapy (patisiran) and ASO therapy

TM (InotersenTM) represent a significant advance in the field of am-

yloidosis. The unique mechanisms of action of inotersenTM and

® patisiran® overcome many limitations of other treatments. Both

are efficacious in hATTR patients with early- and late-onset stages.

Besides, both improve and slow the neuropathy progression. Al-

though RNA therapy and ASO therapy are emerging treatments

for peripheral neuropathy and other neurological disorders, for-

mulation, dosing, and safety monitoring are different than con-

ventional medicines. Thus, additional research is still necessary to

understand the detail mechanism and effectiveness of these pio-

neer therapies when patients with hATTR receive these emerging

therapies. As these pioneering and emerging therapies expand, the

prospect for patients is becoming more promising, offering hope

for a debilitating and life-threatening disease.

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