An evaluation of patisiran: a viable treatment option for transthyretin-related hereditary amyloidosis.
Expert Opin Pharmacother
; 20(18): 2223-2228, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31566422
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neuropatías Amiloides Familiares
/
ARN Interferente Pequeño
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Aspecto:
Patient_preference
Límite:
Humans
Idioma:
En
Revista:
Expert Opin Pharmacother
Asunto de la revista:
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia