Request Demo

Last update 23 Jan 2025

IFNβ x IFNAR

Last update 23 Jan 2025

Basic Info

Related Targets

IFNβIFNAR

Drugs associated with IFNβ x IFNAR

ART-I02

Target

IFNAR x IFNβ

Mechanism

IFNAR agonists [+1]

Active Org.

Academic Medical Center University of Amsterdam [+1]

Originator Org.

MeiraGTx Netherlands BV

Active Indication

Rheumatoid Arthritis

Inactive Indication

Osteoarthritis

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with IFNβ x IFNAR

NCT03445715

/ Unknown statusPhase 1

A Single Dose Clinical Trial to Study the Safety of ART-I02 in Patients With Rheumatoid Arthritis

Start Date03 Jan 2018

Sponsor / Collaborator

MeiraGTx Netherlands BV

NCT02727764

/ Unknown statusPhase 1

A Single Dose Clinical Trial to Study the Safety of ART-I02 in Patients With Arthritis

This study will evaluate the safety and tolerability of a single intra-articular administration of ART-I02 (AAV5.NF-kB.IFN-β), a recombinant adeno-associated virus (AAV) type 2/5 vector in subjects with Rheumatoid Arthritis (RA) or Osteoarthritis (OA) and active arthritis of the carpometacarpal (CMC), metacarpophalangeal (MCP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) joints.

Start Date20 Apr 2017

Sponsor / Collaborator

MeiraGTx Netherlands BV

[+1]

100 Clinical Results associated with IFNβ x IFNAR

100 Translational Medicine associated with IFNβ x IFNAR

0 Patents (Medical) associated with IFNβ x IFNAR

550

Literatures (Medical) associated with IFNβ x IFNAR

03 Feb 2025·Journal of Experimental Medicine

A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity

Article

Author: Bleakley, Kevin ; Turvey, Stuart E. ; Newton, Paul N. ; Chevalier, Veronique ; Sibounheunang, Bountoy ; Tangye, Stuart G. ; Ng, Lisa F.P. ; Thuy, Phung Bich ; Zhang, Qian ; Mansouri, Davood ; Bhattad, Sagar ; Mercado-García, Jesús ; Trouillet-Assant, Sophie ; Al Qureshah, Fahd ; Lortholary, Olivier ; Arias, Andrés A. ; Tayoun, Ahmad Abou ; Chantratita, Wasun ; Aye, Aye Mya Min ; Vinh, Donald C. ; Panha, M. ; Colobran, Roger ; Santy, Ky ; Al-Muhsen, Saleh ; Borghesi, Alessandro ; Aguilar-López, Raúl ; Feldman, Hagit Baris ; Phakhounthong, Khansoudaphone ; Rodríguez-Gallego, Carlos ; El Zein, Loubna ; Bizien, Lucy ; Quyen, Do ; Crabol, Yoann ; Brodin, Petter ; Christodoulou, John ; Rice, Charles M. ; Okada, Satoshi ; Tin, Ommar Swe ; Perez-Tur, Jordi ; Laurent, Denis ; Fakhreddine, Soha ; Fontenille, Didier ; Bunleat, M. ; Chommanam, Danoy ; Linn, Kyaw ; Alcántara-Garduño, Ana Bertha ; Thorball, Christian ; An, Pham Nhat ; Ozcelik, Tayfun ; de Lamballerie, Xavier ; Duvlis, Sotiriјa ; Channa, Mey ; Vongsouvath, Manivanh ; Cobat, Aurélie ; Gorman, Chris ; Phangmanixay, Sommanikhone ; Capelle, Julien ; Tin, Htay Htay ; Meyts, Isabelle ; Le Pen, Jérémie ; Moatti, Jean-Paul ; Pedraza-Sanchez, Sigifredo ; Herrant, Magali ; Condino-Neto, Antonio ; Keles, Sevgi ; Saheb Sharif-Askari, Narjes ; Fellay, Jacques ; Materna, Marie ; Dündar, Munis ; Casanova, Jean-Laurent ; Ferrant, Catherine ; Zabaleta-Martínez, Oscar ; Lau, Yu Lung ; Duval, Xavier ; Herrera, María Teresa ; Anh, Dang Duc ; Durand, Benoit ; Pérot, Philippe ; Ozcelik, Firat ; Tan, Luong Minh ; Flores, Carlos ; Oo, Khin Yi ; Davong, Viengmon ; Hlaing, Chaw Su ; Uddin, Furkan ; Andreakos, Evangelos ; Temel, Şehime Gülsün ; Halwani, Rabih ; Oum, MengHeng ; Resnick, Igor ; Hung, Tran Thi Mai ; Huong, Tran Thi Thu ; de Prost, Nicolas ; Devaux, Christian ; Mayxay, Mayfong ; Mogensen, Trine H. ; Le-voyer, Tom ; Bun, Kimrong ; Debré, Patrice ; Pham, Anh Tuan ; Franco, José Luis ; Sim, M.Kanarith ; Aiuti, Alessandro ; Tarantola, Arnaud ; Gorochov, Guy ; Bolze, Alexandre ; Sedighzadeh, Sahar ; Rosset, Bruno ; Jouan, Marc ; Lam, Nguyen Van ; Renia, Laurent ; Seephone, Malee ; Hagin, David ; Soler-Palacín, Pere ; Jouanguy, Emmanuelle ; Sothy, Heng ; Moncada-Velez, Marcela ; Milisavljevic, Baptiste ; Honnorat, Jérôme ; Phongsavath, Khounthavy ; Leung, Daniel ; Piola, Patrice ; Torktaz, Ibrahim ; Vongsouvath, Malavanh ; Thein, Win ; Hammoud, Hassan ; Duong, Veasna ; Pesole, Graziano ; Bonnet, Pascal ; Seguy, Maud ; Hertzog, Paul J. ; Hien, Nguyen ; Lorenzo, Lazaro ; Béziat, Vivien ; Gregersen, Peter K. ; Novelli, Giuseppe ; Abel, Laurent ; Phuc, Phan Huu ; Zhang, Peng ; Tissot-Dupont, Hervé ; Dubot-Peres, Auey ; Spaan, András N. ; Dussart, Philippe ; Bastard, Paul ; Sbeity, Manal ; Rattanavong, Sayaphet ; Hafner, Lukas ; Hai, Le Thanh ; Tam, Anthony R. ; Thair, Cho ; Vianna, Fernanda Sales Luiz ; Huong, Do Thu ; Eng, Chanreaksmey ; Berkun, Yackov ; Eloit, Marc ; Buchy, Philippe ; Pinto, Anne Laurie ; Hung, Ivan Fan-Ngai ; Thuy, Nguyen Thi Thu ; Lin, Daniel C. ; Vianna, Fernanda ; de Diego, Rebeca Perez ; Murgue, Bernadette ; Lau, Yu-Lung ; Douangnouvong, Anousone ; Zhang, Shen-Ying ; Lecuit, Marc ; Delfraissy, Jean-François ; July, May ; Bousfiha, Ahmed A. ; Bunnakea, Em ; Novelli, Antonio ; Dubot-Pérès, Audrey ; Lago, Magali ; Singh, Neha ; Pommier, Jean-David ; Kyaw, Latt Latt ; de Weerd, Nicole A. ; Puel, Anne ; Shahrooei, Mohammad

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%). Cells heterozygous for these variants display a dominant phenotype in vitro with impaired responses to IFN-α and -ω, but not -β, and viral susceptibility. Negative dominance, rather than haploinsufficiency, accounts for this dominance. Patients heterozygous for these variants are prone to viral diseases, attesting to both the dominance of these variants clinically and the importance of IFN-α and -ω for protective immunity against some viruses.

02 Dec 2024·Protein & Cell

Macrophages suppress cardiac reprogramming of fibroblasts in vivo via IFN-mediated intercellular self-stimulating circuit

Article

Author: Zhao, Yang ; Cai, Yihong ; Yang, Junbo ; Wang, Hao

AbstractDirect conversion of cardiac fibroblasts (CFs) to cardiomyocytes (CMs) in vivo to regenerate heart tissue is an attractive approach. After myocardial infarction (MI), heart repair proceeds with an inflammation stage initiated by monocytes infiltration of the infarct zone establishing an immune microenvironment. However, whether and how the MI microenvironment influences the reprogramming of CFs remains unclear. Here, we found that in comparison with cardiac fibroblasts (CFs) cultured in vitro, CFs that transplanted into infarct region of MI mouse models resisted to cardiac reprogramming. RNA-seq analysis revealed upregulation of interferon (IFN) response genes in transplanted CFs, and subsequent inhibition of the IFN receptors increased reprogramming efficiency in vivo. Macrophage-secreted IFN-β was identified as the dominant upstream signaling factor after MI. CFs treated with macrophage-conditioned medium containing IFN-β displayed reduced reprogramming efficiency, while macrophage depletion or blocking the IFN signaling pathway after MI increased reprogramming efficiency in vivo. Co-IP, BiFC and Cut-tag assays showed that phosphorylated STAT1 downstream of IFN signaling in CFs could interact with the reprogramming factor GATA4 and inhibit the GATA4 chromatin occupancy in cardiac genes. Furthermore, upregulation of IFN-IFNAR-p-STAT1 signaling could stimulate CFs secretion of CCL2/7/12 chemokines, subsequently recruiting IFN-β-secreting macrophages. Together, these immune cells further activate STAT1 phosphorylation, enhancing CCL2/7/12 secretion and immune cell recruitment, ultimately forming a self-reinforcing positive feedback loop between CFs and macrophages via IFN-IFNAR-p-STAT1 that inhibits cardiac reprogramming in vivo. Cumulatively, our findings uncover an intercellular self-stimulating inflammatory circuit as a microenvironmental molecular barrier of in situ cardiac reprogramming that needs to be overcome for regenerative medicine applications.

01 Dec 2024·Current Microbiology

RT-qPCR Analysis of Inflammatory & Apoptotic Factors-Related Gene Expression in ZIKV-Infected IFNAR1−/− Mice

Article

Author: Lin, Xiao Han ; Seo, Sang Heui ; Chowdhury, Dibakar

ZIKV was a mosquito-borne neglected tropical pathogen until it spread into the Pacific and South America, followed by large human outbreaks related to congenital abnormalities in neonates and neurological disorders in adults. The following study used the C57BL/6 IFNAR1 receptor knockout (IFN AR1^-/-) mouse model to understand the role of selected cytokines and apoptotic factors in the pathogenicity of ZIKV strain PRVABC59. Mice infected with 10² particles of Zika viruses died until 9 days post infection. The brain, spleen, and lung were collected from intramuscularly infected mice on day 6 post infection (pi) to quantify the mRNA expression of targeted cytokines and apoptosis-mediated factors by RT-qPCR. Upregulation of IL-6, IL-17α, IFN-α, and IFN-β were found in the brain and lung of infected mice. IFN-γ was also significantly upregulated in the infected brain and spleen. The collective findings from our study indicate that a strong immune response was developed against ZIKV PRVABC59 in the infected mice brain.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis