Abstract
INTRODUCTION: Amyloid transthyretin amyloidosis (ATTR) is a progressive and often fatal disease caused by the buildup of mutated (hereditary ATTR [hATTR]; also known as ATTR variant [ATTRv]) or normal transthyretin (wild-type ATTR) throughout the body. Two new therapies-inotersen, an antisense oligonucleotide therapy, and patisiran, an RNA interference therapy-received marketing authorization and represent a significant advance in the treatment of amyloidosis. Herein, we describe the clinical presentation of ATTR, commonly used procedures in its diagnosis, and current treatment landscape for ATTR, with a focus on hATTR. METHODS: A PubMed search from 2008 to September 2018 was conducted to review the literature on ATTR. RESULTS: Until recently, there have been few treatment options for polyneuropathy of hATTR. Inotersen and patisiran substantially reduce the amyloidogenic precursor protein transthyretin and have demonstrated efficacy in patients with early- and late-stage disease and in slowing or improving neuropathy progression. In contrast, established therapies, such as liver transplantation, typically reserved for patients with early-stage disease, and tafamidis, indicated for the treatment of early-stage disease in Europe, or diflunisal, a nonsteroidal anti-inflammatory drug that is used off-label, are associated with side effects and/or unclear efficacy in certain patient populations. Thus, inotersen and patisiran are positioned to be the preferred therapeutic modalities. CONCLUSIONS: Important differences between inotersen and patisiran, including formulation, dosing, requirements for premedications, and safety monitoring, require an understanding and knowledge of each treatment for informed decision making.
| Original language | English (US) |
|---|---|
| Pages (from-to) | e01371 |
| Journal | Brain and behavior |
| Volume | 9 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2019 |
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Keywords
- amyloid
- hATTR
- inotersen
- patisiran
- transthyretin amyloidosis
ASJC Scopus subject areas
- Behavioral Neuroscience
Cite this
Advances in the treatment of hereditary transthyretin amyloidosis : A review. / Gertz, Morie; Mauermann, Michelle M; Grogan, Martha; Coelho, Teresa.
In: Brain and behavior, Vol. 9, No. 9, 01.09.2019, p. e01371.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Advances in the treatment of hereditary transthyretin amyloidosis
T2 - A review
AU - Gertz, Morie
AU - Mauermann, Michelle M
AU - Grogan, Martha
AU - Coelho, Teresa
PY - 2019/9/1
Y1 - 2019/9/1
N2 - INTRODUCTION: Amyloid transthyretin amyloidosis (ATTR) is a progressive and often fatal disease caused by the buildup of mutated (hereditary ATTR [hATTR]; also known as ATTR variant [ATTRv]) or normal transthyretin (wild-type ATTR) throughout the body. Two new therapies-inotersen, an antisense oligonucleotide therapy, and patisiran, an RNA interference therapy-received marketing authorization and represent a significant advance in the treatment of amyloidosis. Herein, we describe the clinical presentation of ATTR, commonly used procedures in its diagnosis, and current treatment landscape for ATTR, with a focus on hATTR. METHODS: A PubMed search from 2008 to September 2018 was conducted to review the literature on ATTR. RESULTS: Until recently, there have been few treatment options for polyneuropathy of hATTR. Inotersen and patisiran substantially reduce the amyloidogenic precursor protein transthyretin and have demonstrated efficacy in patients with early- and late-stage disease and in slowing or improving neuropathy progression. In contrast, established therapies, such as liver transplantation, typically reserved for patients with early-stage disease, and tafamidis, indicated for the treatment of early-stage disease in Europe, or diflunisal, a nonsteroidal anti-inflammatory drug that is used off-label, are associated with side effects and/or unclear efficacy in certain patient populations. Thus, inotersen and patisiran are positioned to be the preferred therapeutic modalities. CONCLUSIONS: Important differences between inotersen and patisiran, including formulation, dosing, requirements for premedications, and safety monitoring, require an understanding and knowledge of each treatment for informed decision making.
AB - INTRODUCTION: Amyloid transthyretin amyloidosis (ATTR) is a progressive and often fatal disease caused by the buildup of mutated (hereditary ATTR [hATTR]; also known as ATTR variant [ATTRv]) or normal transthyretin (wild-type ATTR) throughout the body. Two new therapies-inotersen, an antisense oligonucleotide therapy, and patisiran, an RNA interference therapy-received marketing authorization and represent a significant advance in the treatment of amyloidosis. Herein, we describe the clinical presentation of ATTR, commonly used procedures in its diagnosis, and current treatment landscape for ATTR, with a focus on hATTR. METHODS: A PubMed search from 2008 to September 2018 was conducted to review the literature on ATTR. RESULTS: Until recently, there have been few treatment options for polyneuropathy of hATTR. Inotersen and patisiran substantially reduce the amyloidogenic precursor protein transthyretin and have demonstrated efficacy in patients with early- and late-stage disease and in slowing or improving neuropathy progression. In contrast, established therapies, such as liver transplantation, typically reserved for patients with early-stage disease, and tafamidis, indicated for the treatment of early-stage disease in Europe, or diflunisal, a nonsteroidal anti-inflammatory drug that is used off-label, are associated with side effects and/or unclear efficacy in certain patient populations. Thus, inotersen and patisiran are positioned to be the preferred therapeutic modalities. CONCLUSIONS: Important differences between inotersen and patisiran, including formulation, dosing, requirements for premedications, and safety monitoring, require an understanding and knowledge of each treatment for informed decision making.
KW - amyloid
KW - hATTR
KW - inotersen
KW - patisiran
KW - transthyretin amyloidosis
UR - http://www.scopus.com/inward/record.url?scp=85072352538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072352538&partnerID=8YFLogxK
U2 - 10.1002/brb3.1371
DO - 10.1002/brb3.1371
M3 - Review article
C2 - 31368669
AN - SCOPUS:85072352538
VL - 9
SP - e01371
JO - Brain and Behavior
JF - Brain and Behavior
SN - 2157-9032
IS - 9
ER -