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Ann Med. 2015;47(8):625-38. doi: 10.3109/07853890.2015.1068949. Epub 2015 Nov 27.

Evolving landscape in the management of transthyretin amyloidosis.

Author information

1
a National Amyloidosis Centre, Royal Free Hospital, University College London , London , UK.
2
b Department of Neurology , Graduate School of Medical Sciences Kumamoto University , Kumamoto , Japan.
3
c Mayo Clinic, Division of Hematology , Rochester, Minnesota, USA.
4
d Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City , Mexico.
5
e National Reference Centre for FAP, APHP, CHU Bicêtre, Université Paris-Sud, INSERM U788 , Paris , France.
6
f Department of Public Health and Clinical Medicine , Umeå University , Umeå , Sweden.

Abstract

Transthyretin (TTR) amyloidosis (ATTR amyloidosis) is a multisystemic, multigenotypic disease resulting from deposition of insoluble ATTR amyloid fibrils in various organs and tissues. Although considered rare, the prevalence of this serious disease is likely underestimated because symptoms can be non-specific 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 late-stage disease. Indeed, enthusiasm for liver transplantation for familial ATTR amyloidosis with polyneuropathy was dampened by poor outcomes among patients with significant neurological deficits or cardiac involvement. Hence, there remains an unmet medical need for new therapies. The TTR stabilizers tafamidis and diflunisal slow disease progression in some patients with ATTR amyloidosis with polyneuropathy, and the postulated synergistic effect 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 significantly reduced with ISIS-TTR(Rx), 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.

KEYWORDS:

Amyloidosis; RNA interference; cardiomyopathies; polyneuropathies; therapeutics; transthyretin

PMID:
26611723
PMCID:
PMC4720049
DOI:
10.3109/07853890.2015.1068949
[Indexed for MEDLINE]
Free PMC Article

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