Abstract
Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is a rare, progressive, fatal multi-systemic disease, autosomal dominantly inherited with heterogeneous clinical phenotype caused by mutations in the TTR gene. Mutations promoting proteolytic remodeling and tetramer dissociation result in fragmented and full-length TTR monomers that misfold, aggregate and deposit at multiple sites (mainly nerves and heart) causing peripheral neuropathy and/or cardiomyopathy. Areas covered: The authors discuss patisiran, the first approved RNA interference-based therapeutic agent that suppresses the circulating levels of the amyloidogenic protein TTR both wild-type and mutant. This compound demonstrated a safe clinical profile in phase I and II studies and showed a significant clinical effect in a phase III (APOLLO) trial in ATTRv patients. An open-label-extension study is still underway but, based on the positive results, the regulatory agencies granted approval for the treatment of ATTRv with polyneuropathy in Stage I and II. Expert opinion: The patisiran program has demonstrated that substantial TTR concentration reduction is associated with significant and sustained improvement in polyneuropathy scores, quality-of-life profile and several outcome measures that capture the systemic burden of the disease. The drug resulted safe also in long term follow-up studies while its efficacy for ATTR with cardiomyopathy is under investigation.
| Original language | English |
|---|---|
| Journal | Expert Opinion on Pharmacotherapy |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2019 |
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Keywords
- cardiomiopathy
- hereditary transthyretin mediated amyloidosis
- Patisiran
- peripheral neuropathy
- RNA interference
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
An evaluation of patisiran : a viable treatment option for transthyretin-related hereditary amyloidosis. / Milani, Paolo; Mussinelli, Roberta; Perlini, Stefano; Palladini, Giovanni; Obici, Laura.
In: Expert Opinion on Pharmacotherapy, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An evaluation of patisiran
T2 - a viable treatment option for transthyretin-related hereditary amyloidosis
AU - Milani, Paolo
AU - Mussinelli, Roberta
AU - Perlini, Stefano
AU - Palladini, Giovanni
AU - Obici, Laura
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is a rare, progressive, fatal multi-systemic disease, autosomal dominantly inherited with heterogeneous clinical phenotype caused by mutations in the TTR gene. Mutations promoting proteolytic remodeling and tetramer dissociation result in fragmented and full-length TTR monomers that misfold, aggregate and deposit at multiple sites (mainly nerves and heart) causing peripheral neuropathy and/or cardiomyopathy. Areas covered: The authors discuss patisiran, the first approved RNA interference-based therapeutic agent that suppresses the circulating levels of the amyloidogenic protein TTR both wild-type and mutant. This compound demonstrated a safe clinical profile in phase I and II studies and showed a significant clinical effect in a phase III (APOLLO) trial in ATTRv patients. An open-label-extension study is still underway but, based on the positive results, the regulatory agencies granted approval for the treatment of ATTRv with polyneuropathy in Stage I and II. Expert opinion: The patisiran program has demonstrated that substantial TTR concentration reduction is associated with significant and sustained improvement in polyneuropathy scores, quality-of-life profile and several outcome measures that capture the systemic burden of the disease. The drug resulted safe also in long term follow-up studies while its efficacy for ATTR with cardiomyopathy is under investigation.
AB - Introduction: Hereditary transthyretin-mediated amyloidosis (ATTRv; v for variant) is a rare, progressive, fatal multi-systemic disease, autosomal dominantly inherited with heterogeneous clinical phenotype caused by mutations in the TTR gene. Mutations promoting proteolytic remodeling and tetramer dissociation result in fragmented and full-length TTR monomers that misfold, aggregate and deposit at multiple sites (mainly nerves and heart) causing peripheral neuropathy and/or cardiomyopathy. Areas covered: The authors discuss patisiran, the first approved RNA interference-based therapeutic agent that suppresses the circulating levels of the amyloidogenic protein TTR both wild-type and mutant. This compound demonstrated a safe clinical profile in phase I and II studies and showed a significant clinical effect in a phase III (APOLLO) trial in ATTRv patients. An open-label-extension study is still underway but, based on the positive results, the regulatory agencies granted approval for the treatment of ATTRv with polyneuropathy in Stage I and II. Expert opinion: The patisiran program has demonstrated that substantial TTR concentration reduction is associated with significant and sustained improvement in polyneuropathy scores, quality-of-life profile and several outcome measures that capture the systemic burden of the disease. The drug resulted safe also in long term follow-up studies while its efficacy for ATTR with cardiomyopathy is under investigation.
KW - cardiomiopathy
KW - hereditary transthyretin mediated amyloidosis
KW - Patisiran
KW - peripheral neuropathy
KW - RNA interference
UR - http://www.scopus.com/inward/record.url?scp=85074001507&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074001507&partnerID=8YFLogxK
U2 - 10.1080/14656566.2019.1671352
DO - 10.1080/14656566.2019.1671352
M3 - Article
C2 - 31566422
AN - SCOPUS:85074001507
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
SN - 1465-6566
ER -