Repository logo
 
Publication

Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis

2016-06Journal article Open access
Simple item page
dc.contributor.authorCoelho, T.
dc.contributor.authorMerlini, G.
dc.contributor.authorBulawa, C.
dc.contributor.authorFleming, J.
dc.contributor.authorJudge, D.
dc.contributor.authorKelly, J.
dc.contributor.authorMaurer, M.
dc.contributor.authorPlanté-Bordeneuve, V.
dc.contributor.authorLabaudinière, R.
dc.contributor.authorMundayat, R.
dc.contributor.authorRiley, S.
dc.contributor.authorLombardo, I.
dc.contributor.authorHuertas, P.
dc.date.accessioned2017-07-10T15:01:05Z
dc.date.available2017-07-10T15:01:05Z
dc.date.issued2016-06
dc.description.abstractTransthyretin (TTR) transports the retinol-binding protein-vitamin A complex and is a minor transporter of thyroxine in blood. Its tetrameric structure undergoes rate-limiting dissociation and monomer misfolding, enabling TTR to aggregate or to become amyloidogenic. Mutations in the TTR gene generally destabilize the tetramer and/or accelerate tetramer dissociation, promoting amyloidogenesis. TTR-related amyloidoses are rare, fatal, protein-misfolding disorders, characterized by formation of soluble aggregates of variable structure and tissue deposition of amyloid. The TTR amyloidoses present with a spectrum of manifestations, encompassing progressive neuropathy and/or cardiomyopathy. Until recently, the only accepted treatment to halt progression of hereditary TTR amyloidosis was liver transplantation, which replaces the hepatic source of mutant TTR with the less amyloidogenic wild-type TTR. Tafamidis meglumine is a rationally designed, non-NSAID benzoxazole derivative that binds with high affinity and selectivity to TTR and kinetically stabilizes the tetramer, slowing monomer formation, misfolding, and amyloidogenesis. Tafamidis is the first pharmacotherapy approved to slow the progression of peripheral neurologic impairment in TTR familial amyloid polyneuropathy. Here we describe the mechanism of action of tafamidis and review the clinical data, demonstrating that tafamidis treatment slows neurologic deterioration and preserves nutritional status, as well as quality of life in patients with early-stage Val30Met amyloidosis.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNeurol Ther. 2016 Jun;5(1):1-25pt_PT
dc.identifier.doi10.1007/s40120-016-0040-xpt_PT
dc.identifier.issn2193-6536
dc.identifier.issn2193-8253
dc.identifier.urihttp://hdl.handle.net/10400.16/2141
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Healthcarept_PT
dc.relation.publisherversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919130/pdf/40120_2016_Article_40.pdfpt_PT
dc.subjectFamilial amyloid cardiomyopathypt_PT
dc.subjectFamilial amyloid polyneuropathypt_PT
dc.subjectHereditary TTR amyloid cardiomyopathypt_PT
dc.subjectPharmacologypt_PT
dc.subjectSenile systemic amyloidosispt_PT
dc.subjectTherapeutic usept_PT
dc.subjectWild-type TTR amyloidosispt_PT
dc.titleMechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceNew Zealandpt_PT
oaire.citation.endPage25pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleNeurology and Therapypt_PT
oaire.citation.volume5pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Mechanism of Action and Clinical Application of Tafamidis.pdf
Size:
1.28 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.35 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

SNF - Artigos publicados em revistas indexadas na Pubmed/Medline