(Human apotransferrin(Prothya Biosolutions)) - 药物靶点：TFR2 x TfR1_在研适应症：先天性无转铁蛋白血症_专利_临床

概要

基本信息

药物类型

蛋白类药物

别名-

靶点

TFR2 x TfR1

作用机制

TFR2激动剂(transferrin receptor 2 agonists)、TfR1刺激剂(转铁蛋白受体1刺激剂)

治疗领域

遗传病与畸形内分泌与代谢疾病其他疾病

在研适应症

先天性无转铁蛋白血症

非在研适应症-

原研机构

Prothya Biosolutions Netherlands

在研机构

Prothya Biosolutions Netherlands

非在研机构-

最高研发阶段临床2/3期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

关联

4

项与 Human apotransferrin(Prothya Biosolutions) 相关的临床试验

NCT03993613 / Terminated临床2期

Efficacy and Safety of Human Apotransferrin in Patients With β-thalassemia Intermedia

The aim of the trial is to study the effect of apotransferrin administration in patients suffering from β-thalassemia intermedia in order to restore the erythropoiesis as reflected by enhanced haemoglobin levels or reduced transfusion dependency.

开始日期2019-03-21

申办/合作机构

Prothya Biosolutions Netherlands

EUCTR2014-001936-12-NL / Not yet recruiting临床2期

Efficacy and Safety of human apotransferrin in patients with ß-thalassemia - Apotransferrin in patients with ß-thalassemia

开始日期2019-02-11

申办/合作机构

Sanquin Plasma Products BV初创企业

EUCTR2009-017409-13-DE / Unknown status临床2期

Dose escalating study to evaluate pharmacokinetics, efficacy and safety of apotransferrin in atransferrinemia patients - Apotransferrin replacement in atransferrinemia

开始日期2011-05-25

申办/合作机构

Prothya Biosolutions Netherlands BV

100 项与 Human apotransferrin(Prothya Biosolutions) 相关的临床结果

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100 项与 Human apotransferrin(Prothya Biosolutions) 相关的转化医学

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100 项与 Human apotransferrin(Prothya Biosolutions) 相关的专利（医药）

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149

项与 Human apotransferrin(Prothya Biosolutions) 相关的文献（医药）

2023-01-01·Transfusion Medicine and Hemotherapy

Circulating Iron in Patients with Sickle Cell Disease Mediates the Release of Neutrophil Extracellular Traps

Article

作者: Luken, Brenda M ; Biemond, Bart J ; Van Avondt, Kristof ; Schimmel, Marein ; van Mierlo, Gerard ; Nur, Erfan ; Zeerleder, Sacha ; Bulder, Ingrid ; van Bruggen, Robin

Introduction: Neutrophils promote chronic inflammation and release neutrophil extracellular traps (NETs) that can drive inflammatory responses. Inflammation influences progression of sickle cell disease (SCD), and a role for NETs has been suggested in the onset of vaso-occlusive crisis (VOC). We aimed to identify factors in the circulation of these patients that provoke NET release, with a focus on triggers associated with hemolysis. Methods: Paired serum and plasma samples during VOC and steady state of 18 SCD patients (HbSS/HbSβ0-thal and HbSC/HbSβ+-thal) were collected. Cell-free heme, hemopexin, and labile plasma iron have been measured in the plasma samples of the SCD patients. NETs formation by human neutrophils from healthy donors induced by serum of SCD patients was studied using confocal microscopy and staining for extracellular DNA using Sytox, followed by quantification of surface coverage using ImageJ. Results: Eighteen patients paired samples obtained during VOC and steady state were available (11 HbSS/HbSβ0-thal and 7 HbSC/HbSβ+-thal). We observed high levels of systemic heme and iron, concomitant with low levels of the heme-scavenger hemopexin in sera of patients with SCD, both during VOC and in steady state. In our in vitro experiments, neutrophils released NETs when exposed to sera from SCD patients. The release of NETs was associated with high levels of circulating iron in these sera. Although hemin triggered NET formation in vitro, addition of hemopexin to scavenge heme did not suppress NET release in SCD sera. By contrast, the iron scavengers deferoxamine and apotransferrin attenuated NET formation in a significant proportion of SCD sera. Discussion: Our results suggest that redox-active iron in the circulation of non-transfusion-dependent SCD patients activates neutrophils to release NETs, and hence, exerts a direct pro-inflammatory effect. Thus, we propose that chelation of iron requires further investigation as a therapeutic strategy in SCD.

2022-02-01·British Journal of Haematology

Red blood cell transfusion‐induced non‐transferrin‐bound iron promotes Pseudomonas aeruginosa biofilms in human sera and mortality in catheterized mice

Article

作者: Prestia, Kevin ; Bandyopadhyay, Sheila ; La Carpia, Francesca ; Slate, Andrea ; Hod, Eldad A. ; Godbey, Elizabeth A. ; Francis, Kevin P. ; Wojczyk, Boguslaw S.

SummaryTransfusion of storage‐damaged red blood cells (RBCs) increases non‐transferrin‐bound iron (NTBI) levels in humans. This can potentially enhance virulence of microorganisms. In this study, Pseudomonas aeruginosa replication and biofilm production in vitro correlated with NTBI levels of transfused subjects (R2 = 0·80; P < 0·0001). Transfusion of stored RBCs into catheterized mice enhanced P. aeruginosa virulence and mortality in vivo, while pre‐administration of apotransferrin reduced NTBI levels improving survival (69% vs 27% mortality; P < 0·05). These results suggest that longer RBC storage, by modulating the bioavailability of iron, may increase the risk of P. aeruginosa biofilm‐related infections in transfused patients.

2021-12-10·Hematology3区 · 教育学

β-Thalassemia: evolving treatment options beyond transfusion and iron chelation

3区 · 教育学

Review

作者: Esrick, Erica B. ; Langer, Arielle L.

AbstractAfter years of reliance on transfusion alone to address anemia and suppress ineffective erythropoiesis in β-thalassemia, many new therapies are now in development. Luspatercept, a transforming growth factor–β inhibitor, has demonstrated efficacy in reducing ineffective erythropoiesis, improving anemia, and possibly reducing iron loading. However, many patients do not respond to luspatercept, so additional therapeutics are needed. Several medications in development aim to induce hemoglobin F (HbF): sirolimus, benserazide, and IMR-687 (a phosphodiesterase 9 inhibitor). Another group of agents seeks to ameliorate ineffective erythropoiesis and improve anemia by targeting abnormal iron metabolism in thalassemia: apotransferrin, VIT-2763 (a ferroportin inhibitor), PTG-300 (a hepcidin mimetic), and an erythroferrone antibody in early development. Mitapivat, a pyruvate kinase activator, represents a unique mechanism to mitigate ineffective erythropoiesis. Genetically modified autologous hematopoietic stem cell transplantation offers the potential for lifelong transfusion independence. Through a gene addition approach, lentiviral vectors have been used to introduce a β-globin gene into autologous hematopoietic stem cells. One such product, betibeglogene autotemcel (beti-cel), has reached phase 3 trials with promising results. In addition, 2 gene editing techniques (CRISPR-Cas9 and zinc-finger nucleases) are under investigation as a means to silence BCL11A to induce HbF with agents designated CTX001 and ST-400, respectively. Results from the many clinical trials for these agents will yield results in the next few years, which may end the era of relying on transfusion alone as the mainstay of thalassemia therapy.

100 项与 Human apotransferrin(Prothya Biosolutions) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
先天性无转铁蛋白血症	临床3期	意大利	Prothya Biosolutions Netherlands	2010-12-01
先天性无转铁蛋白血症	临床3期	西班牙	Prothya Biosolutions Netherlands	2010-12-01
先天性无转铁蛋白血症	临床3期	德国	Prothya Biosolutions Netherlands	2010-12-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASH2023	临床2/3期	先天性无转铁蛋白血症	5	Human apotransferrin	艱遞獵顧蓋積繭簾醖觸(積餘積襯繭糧鏇遞廠顧) = 餘壓窪製夢餘鹹觸廠餘觸獵夢糧獵蓋廠遞壓蓋 (鑰範衊願鑰製艱願願糧 )	积极	2023-12-11