Abstract
Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is an underdiagnosed, progressive, and fatal multisystemic disease with a heterogenous clinical phenotype that is caused by TTR gene mutations that destabilize the TTR protein, resulting in its misfolding, aggregation, and deposition in tissues throughout the body. Areas covered: Inotersen, an antisense oligonucleotide inhibitor, was recently approved in the United States and Europe for the treatment of the polyneuropathy of ATTRv based on the positive results obtained in the pivotal phase 3 trial, NEURO-TTR. This review will discuss the mechanism of action of inotersen and its pharmacology, clinical efficacy, and safety and tolerability. A PubMed search using the terms ‘inotersen,’ ‘AG10,’ ‘antisense oligonucleotide,’ ‘hereditary transthyretin amyloidosis,’ ‘familial amyloid polyneuropathy,’ and ‘familial amyloid cardiomyopathy’ was performed, and the results were screened for the most relevant English language publications. The bibliographies of all retrieved articles were manually searched to identify additional studies of relevance. Expert opinion: Inotersen targets the disease-forming protein, TTR, and has been shown to improve quality of life and neuropathy progression in patients with stage 1 or 2 ATTRv with polyneuropathy. Inotersen is well tolerated, with a manageable safety profile through regular monitoring for the development of glomerulonephritis or thrombocytopenia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 701-711 |
| Number of pages | 11 |
| Journal | Expert Review of Clinical Pharmacology |
| Volume | 12 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 3 2019 |
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Keywords
- cardiomyopathy
- Hereditary transthyretin-mediated amyloidosis
- inotersen
- peripheral neuropathy
- ribonucleic acid interference
- transthyretin
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology (medical)
Cite this
Inotersen for the treatment of adults with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis. / Gertz, Morie A.; Scheinberg, Morton; Waddington-Cruz, Márcia; Heitner, Stephen; Karam, Chafic; Drachman, Brian; Khella, Sami; Whelan, Carol; Obici, Laura.
In: Expert Review of Clinical Pharmacology, Vol. 12, No. 8, 03.08.2019, p. 701-711.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inotersen for the treatment of adults with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis
AU - Gertz, Morie A.
AU - Scheinberg, Morton
AU - Waddington-Cruz, Márcia
AU - Heitner, Stephen
AU - Karam, Chafic
AU - Drachman, Brian
AU - Khella, Sami
AU - Whelan, Carol
AU - Obici, Laura
PY - 2019/8/3
Y1 - 2019/8/3
N2 - Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is an underdiagnosed, progressive, and fatal multisystemic disease with a heterogenous clinical phenotype that is caused by TTR gene mutations that destabilize the TTR protein, resulting in its misfolding, aggregation, and deposition in tissues throughout the body. Areas covered: Inotersen, an antisense oligonucleotide inhibitor, was recently approved in the United States and Europe for the treatment of the polyneuropathy of ATTRv based on the positive results obtained in the pivotal phase 3 trial, NEURO-TTR. This review will discuss the mechanism of action of inotersen and its pharmacology, clinical efficacy, and safety and tolerability. A PubMed search using the terms ‘inotersen,’ ‘AG10,’ ‘antisense oligonucleotide,’ ‘hereditary transthyretin amyloidosis,’ ‘familial amyloid polyneuropathy,’ and ‘familial amyloid cardiomyopathy’ was performed, and the results were screened for the most relevant English language publications. The bibliographies of all retrieved articles were manually searched to identify additional studies of relevance. Expert opinion: Inotersen targets the disease-forming protein, TTR, and has been shown to improve quality of life and neuropathy progression in patients with stage 1 or 2 ATTRv with polyneuropathy. Inotersen is well tolerated, with a manageable safety profile through regular monitoring for the development of glomerulonephritis or thrombocytopenia.
AB - Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is an underdiagnosed, progressive, and fatal multisystemic disease with a heterogenous clinical phenotype that is caused by TTR gene mutations that destabilize the TTR protein, resulting in its misfolding, aggregation, and deposition in tissues throughout the body. Areas covered: Inotersen, an antisense oligonucleotide inhibitor, was recently approved in the United States and Europe for the treatment of the polyneuropathy of ATTRv based on the positive results obtained in the pivotal phase 3 trial, NEURO-TTR. This review will discuss the mechanism of action of inotersen and its pharmacology, clinical efficacy, and safety and tolerability. A PubMed search using the terms ‘inotersen,’ ‘AG10,’ ‘antisense oligonucleotide,’ ‘hereditary transthyretin amyloidosis,’ ‘familial amyloid polyneuropathy,’ and ‘familial amyloid cardiomyopathy’ was performed, and the results were screened for the most relevant English language publications. The bibliographies of all retrieved articles were manually searched to identify additional studies of relevance. Expert opinion: Inotersen targets the disease-forming protein, TTR, and has been shown to improve quality of life and neuropathy progression in patients with stage 1 or 2 ATTRv with polyneuropathy. Inotersen is well tolerated, with a manageable safety profile through regular monitoring for the development of glomerulonephritis or thrombocytopenia.
KW - cardiomyopathy
KW - Hereditary transthyretin-mediated amyloidosis
KW - inotersen
KW - peripheral neuropathy
KW - ribonucleic acid interference
KW - transthyretin
UR - http://www.scopus.com/inward/record.url?scp=85068527064&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068527064&partnerID=8YFLogxK
U2 - 10.1080/17512433.2019.1635008
DO - 10.1080/17512433.2019.1635008
M3 - Article
VL - 12
SP - 701
EP - 711
JO - Expert Review of Clinical Pharmacology
JF - Expert Review of Clinical Pharmacology
SN - 1751-2433
IS - 8
ER -