Evidence map›Paper›PMID 26894299›Full record

ReviewNeurology and therapy2016

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

Teresa Coelho, Giampaolo Merlini, Christine E Bulawa, James A Fleming, Daniel P Judge, Jeffery W Kelly, Mathew S Maurer, Violaine Planté-Bordeneuve, Richard Labaudinière, Rajiv Mundayat and 3 more

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neurology and therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 2 pooled it
8.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 180 citations in OpenAlex.

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  19. Initiation of transthyretin aggregation at neutral pH by fluid agitation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Review

15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 8 institutions in 4 countries.

Teresa CoelhoHospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal. tcoelho@netcabo.pt.
Giampaolo MerliniFoundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
Christine E BulawaPfizer Rare Disease Research Unit, Cambridge, MA, USA.
James A FlemingPfizer Rare Disease Research Unit, Cambridge, MA, USA.
Daniel P JudgeJohns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeffery W KellyThe Scripps Research Institute, La Jolla, CA, USA.
Mathew S MaurerColumbia University College of Physicians and Surgeons, New York, NY, USA.
Violaine Planté-BordeneuveCHU Henri Mondor, Créteil, France.
Richard LabaudinièreLabaudiniere Consulting LLC, Lewes, DE, USA.
Rajiv MundayatPfizer Inc., New York, NY, USA.
Steve RileyPfizer Inc., New York, NY, USA.
Ilise LombardoFORUM Pharmaceuticals, Watertown, MA, USA.
Pedro HuertasMassachusetts General and McLean Hospitals, Harvard Medical School, Boston, MA, USA.
Pfizer (United States) · USCentre Hospitalier Universitaire Henri-Mondor · FRCentro Hospitalar do Porto · PTColumbia University · USHarvard University · USIstituti di Ricovero e Cura a Carattere Scientifico · ITJohns Hopkins University · USScripps Research Institute · US

Funding

Midcareer Mentoring Award for Patient Oriented Research in Geriatric CardiologyK24AG036778 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MAURER, MATHEW S · 2010 to 2020
$1.6M
NIA NIH HHS K24 AG036778
6 · The paper itself

Abstract

Transthyretin (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.

Indexed as

Familial amyloid cardiomyopathyFamilial amyloid polyneuropathyHereditary TTR amyloid cardiomyopathyPharmacologySenile systemic amyloidosisTherapeutic useWild-type TTR amyloidosis

Identifiers

PMID26894299
PMCPMC4919130
OpenAlexW2295890540

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.