Evidence map›Paper›PMID 33131252›Full record

ArticleHaematologica2020

Novel aptamer to von Willebrand factor A1 domain (TAGX-0004) shows total inhibition of thrombus formation superior to ARC1779 and comparable to caplacizumab.

Kazuya Sakai, Tatsuhiko Someya, Kaori Harada, Hideo Yagi, Taei Matsui, Masanori Matsumoto

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

Article in Haematologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Kazuya SakaiDepartment of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
Tatsuhiko SomeyaTAGCyx Biotechnologies Inc, Tokyo, Japan.
Kaori HaradaTAGCyx Biotechnologies Inc, Tokyo, Japan.
Hideo YagiDepartment of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
Taei MatsuiClinical Laboratory Medicine, Fujita Health University School of Medical Sciences, Toyoake, Japan.
Masanori MatsumotoDepartment of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
Nara Medical University · JPTagCyx Biotechnologies (Japan) · JPFujita Health University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

von Willebrand factor (VWF) is a blood glycoprotein that plays an important role in platelet thrombus formation through interaction between its A1 domain and platelet glycoprotein Ib. ARC1779, an aptamer to the VWF A1 domain, was evaluated in a clinical trial for acquired thrombotic thrombocytopenic purpura (aTTP). Subsequently, caplacizumab, an anti-VWF A1 domain nanobody, was approved for aTTP in Europe and the United States. We recently developed a novel DNA aptamer, TAGX-0004, to the VWF A1 domain; it contains an artificial base and demonstrates high affinity for VWF. To compare the effects of these three agents on VWF A1, their ability to inhibit ristocetin- or botrocetin-induced platelet aggregation under static conditions was analyzed, and the inhibition of thrombus formation under high shear stress was investigated in a microchip flow chamber system. In both assays, TAGX-0004 showed stronger inhibition than ARC1779, and had comparable inhibitory effects to caplacizumab. The binding sites of TAGX-0004 and ARC1779 were analyzed with surface plasmon resonance performed using alanine scanning mutagenesis of the VWF A1 domain. An electrophoretic mobility shift assay showed that R1395 and R1399 in the A1 domain bound to both aptamers. R1287, K1362, and R1392 contributed to ARC1779 binding, and F1366 was essential for TAGX-0004 binding. Surface plasmon resonance analysis of the binding sites of caplacizumab identified five amino acids in the VWF A1 domain (K1362, R1392, R1395, R1399, and K1406). These results suggested that TAGX-0004 possessed better pharmacological properties than caplacizumab in vitro and might be similarly promising for aTTP treatment.

Indexed as

Aptamers, NucleotideThrombosisEuropeHumansPlatelet Glycoprotein GPIb-IX ComplexSingle-Domain Antibodiesvon Willebrand FactorAptamers, NucleotideARC 1779caplacizumabPlatelet Glycoprotein GPIb-IX ComplexSingle-Domain Antibodiesvon Willebrand Factor

Identifiers

PMID33131252
PMCPMC7604614
OpenAlexW2996469805

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.