Delving into the Latest Updates on Human apotransferrin(Prothya Biosolutions) with Synapse

Overview

Basic Info

Drug Type

Protein drugs

Synonyms-

Target

TFR2 x TfR1

Mechanism

TFR2 agonists(transferrin receptor 2 agonists), TfR1 stimulants(Transferrin receptor protein 1 stimulants)

Therapeutic Areas

Congenital DisordersEndocrinology and Metabolic DiseaseOther Diseases

Active Indication

Congenital Atransferrinemia

Inactive Indication

Beta-Thalassemia

Originator Organization

Prothya Biosolutions Netherlands B.V.

Active Organization

Prothya Biosolutions Netherlands B.V.

Inactive Organization-

Drug Highest PhasePhase 2/3

First Approval Date-

RegulationOrphan Drug (EU)

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The purpose of this study is to establish the safety of the combined drug approach (anti-thrombin III, infliximab, apotransferrin, human recombinant erythropoietin beta, C1-inhibitor, glutathione, alfa-tocopherol, melatonin and epoprostenol)aimed to reduce ischemia-reperfusion injury during liver transplantation in eligible recipients.

Start Date01 Aug 2013

Sponsor / Collaborator-

EUCTR2009-017409-13-DE / Not yet recruitingPhase 2

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

Start Date25 May 2011

Sponsor / Collaborator

Prothya Biosolutions Netherlands B.V.

100 Clinical Results associated with Human apotransferrin(Prothya Biosolutions)

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100 Translational Medicine associated with Human apotransferrin(Prothya Biosolutions)

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100 Patents (Medical) associated with Human apotransferrin(Prothya Biosolutions)

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150

Literatures (Medical) associated with Human apotransferrin(Prothya Biosolutions)

01 Jan 2023·Transfusion Medicine and Hemotherapy

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

Article

Author: 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.

01 Feb 2022·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

Author: Prestia, Kevin ; La Carpia, Francesca ; Bandyopadhyay, Sheila ; 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.

10 Dec 2021·HematologyQ3 · EDUCATION

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

Q3 · EDUCATION

Review

Author: 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 Deals associated with Human apotransferrin(Prothya Biosolutions)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Beta-Thalassemia	Phase 3	NL	Prothya Biosolutions Netherlands B.V.	21 Mar 2019
Congenital Atransferrinemia	Phase 3	DE	Prothya Biosolutions Netherlands B.V.	01 Dec 2010
Congenital Atransferrinemia	Phase 3	IT	Prothya Biosolutions Netherlands B.V.	01 Dec 2010
Congenital Atransferrinemia	Phase 3	ES	Prothya Biosolutions Netherlands B.V.	01 Dec 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EHA2024	Phase 2/3	Congenital Atransferrinemia	5	Human Apotransferrin	osykyspbdg(iairdzcutq) = slightly lower than the mean dose-normalized AUC∞ at a single dose in year 1, indicating non-linearity swqstddacl (vujhmfpslm ) View more	Positive	14 May 2024
EHA2024	Phase 2/3	Congenital Atransferrinemia	5	Human Apotransferrin		Positive	14 May 2024
ASH2023	Phase 2/3	Congenital Atransferrinemia	5	Human apotransferrin	jhoertgawa(fblbcjepho) = mblkjmqziv apfzxhzwbf (nmqacwcfwd )	Positive	11 Dec 2023