Evolving landscape in the management of transthyretin amyloidosis

Philip N. Hawkins, Yukio Ando, Angela Dispenzeri, Alejandra Gonzalez-Duarte, David Adams, Ole B. Suhr

Research output: Contribution to journalReview article

86 Scopus citations

Abstract

Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fi brils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specifi c and diagnosis largely relies on amyloid detection in tissue biopsies. Treatment is guided by which tissues/organs are involved, although therapeutic options are limited for patients with latestage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with signifi cant neurological defi cits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and difl unisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic eff ect of doxycycline and tauroursodeoxycholic acid on dissolution of amyloid is under investigation. Another therapeutic approach is to reduce production of the amyloidogenic protein, TTR. Plasma TTR concentration can be signifi cantly reduced with ISIS-TTRRx, an investigational antisense oligonucleotide-based drug, or with patisiran and revusiran, which are investigational RNA interference-based therapeutics that target the liver. The evolving treatment landscape for ATTR amyloidosis brings hope for further improvements in clinical outcomes for patients with this debilitating disease.

Original languageEnglish (US)
Pages (from-to)625-638
Number of pages14
JournalAnnals of Medicine
Volume47
Issue number8
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Amyloidosis
  • Cardiomyopathies
  • Polyneuropathies
  • RNA interference
  • Therapeutics
  • Transthyretin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hawkins, P. N., Ando, Y., Dispenzeri, A., Gonzalez-Duarte, A., Adams, D., & Suhr, O. B. (2015). Evolving landscape in the management of transthyretin amyloidosis. Annals of Medicine, 47(8), 625-638. https://doi.org/10.3109/07853890.2015.1068949