Last update 01 Nov 2024

WSPAR

Last update 01 Nov 2024

Basic Info

Synonyms

lncTCF7, TCONS_00009511-XLOC_004555, WNT signaling pathway activating non-coding RNA

+ [1]

Introduction-

Drugs associated with WSPAR

Restoret

Target

WSPAR

Mechanism

WSPAR inhibitors

Active Org.

Eyebiotech Ltd.

Originator Org.

Eyebiotech Ltd.

Active Indication

Diabetic macular oedema [+2]

Inactive Indication-

Drug Highest PhasePhase 2/3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with WSPAR

NCT06571045 / RecruitingPhase 2/3

A Randomized, Double-Masked, Multi-Center, 3-Arm Pivotal Phase 2/3 Study to Evaluate The Efficacy and Safety of Intravitreal EYE103 Compared With Intravitreal Ranibizumab (0.5mg) in Participants With Diabetic Macular Edema

EYE-RES-102 is a randomized, double masked pivotal study to evaluate the efficacy and safety of 2 dose levels of EYE103 in comparison with the active control, ranibizumab, in patients with diabetic macular edema (DME)
In the first year, all 3 treatment groups will be treated every 4 weeks with either EYE103 or ranibizumab. Beginning at Year 2, the frequency of treatment for participants will shift based on a personalized treatment interval algorithm.
Approximately 960 participants will be entered in the study.

Start Date14 Aug 2024

Sponsor / Collaborator

Eyebiotech Ltd.

NCT05919693 / CompletedPhase 1/2

A 2-part Study Consisting of an Open-label Multiple Ascending Dose (MAD) Safety Study, and a Dose-finding Single-masked Comparative Safety and Preliminary Efficacy Study of Intravitreal (IVT) EYE103 in a Mixed Population of Participants With Diabetic Macular Edema (DME) or Neovascular Age-related Macular Degeneration (NVAMD)

EYE103-101 is a 2-part study assessing safety and preliminary efficacy of EYE103 in patients with diabetic macular edema (DME) given as monotherapy or neovascular macular degeneration (NVAMD) given in combination with anti-VEGF.
In the first part, termed the multiple ascending dose (MAD) portion of study, the safety of EYE103 will be assessed at escalating doses. Approximately 12 participants will be entered in this part of the study.
In the second part of the study, called the dose finding part two doses of EYE103 will be selected and their effectiveness will be compared. Approximately 80 participants will be entered in this part of the study.

Start Date12 Jun 2023

Sponsor / Collaborator

Eyebiotech Ltd.

100 Clinical Results associated with WSPAR

100 Translational Medicine associated with WSPAR

0 Patents (Medical) associated with WSPAR

Literatures (Medical) associated with WSPAR

01 Dec 2020·Cancer Cell InternationalQ3 · MEDICINE

Identification of prognosis-related genes and construction of multi-regulatory networks in pancreatic cancer microenvironment by bioinformatics analysis

Q3 · MEDICINE

ArticleOA

Author: Liao, Quan ; Zhao, Yupei ; Zhang, Ronghua ; Li, Tong ; Liu, Qiaofei

AbstractBackgroundAs one of the most lethal cancers, pancreatic cancer has been characterized by abundant supportive tumor-stromal cell microenvironment. Although the advent of tumor-targeted immune checkpoint blockers has brought light to patients with other cancers, its clinical efficacy in pancreatic cancer has been greatly limited due to the protective stroma. Thus, it is urgent to find potential new targets and establish multi-regulatory networks to predict patient prognosis and improve treatment.MethodsWe followed a strategy based on mining the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm to obtain the immune scores and stromal scores. Differentially expressed genes (DEGs) associated with poor overall survival of pancreatic cancer were screened from a TCGA cohort. By comparing global gene expression with high vs. low immune scores and subsequent Kaplan–Meier analysis, DEGs that significantly correlated with poor overall survival of pancreatic cancer in TCGA cohort were extracted. After constructing the protein–protein interaction network using STRING and limiting the genes within the above DEGs, we utilized RAID 2.0, TRRUST v2 database and degree and betweenness analysis to obtain non-coding RNA (ncRNA)-pivotal nodes and transcription factor (TF)-pivotal nodes. Finally, multi-regulatory networks have been constructed and pivotal drugs with potential benefit for pancreatic cancer patients were obtained by screening in the DrugBank.ResultsIn this study, we obtained 246 DEGs that significantly correlated with poor overall survival of pancreatic cancer in the TCGA cohort. With the advent of 38 ncRNA-pivotal nodes and 7 TF-pivotal nodes, the multi-factor regulatory networks were constructed based on the above pivotal nodes. Prognosis-related genes and factors such as HCAR3, PPY, RFWD2, WSPAR and Amcinonide were screened and investigated.ConclusionThe multi-regulatory networks constructed in this study are not only beneficial to improve treatment and evaluate patient prognosis with pancreatic cancer, but also favorable for implementing early diagnosis and personalized treatment. It is suggested that these factors may play an essential role in the progression of pancreatic cancer.

12 Jul 2019·Oncology Research Featuring Preclinical and Clinical Cancer TherapeuticsQ2 · MEDICINE

1,25(OH)2D3 Attenuates IL-1β-Induced Epithelial-to-Mesenchymal Transition Through Inhibiting the Expression of lncTCF7

Q2 · MEDICINE

Article

Author: Zuo, Shuai ; Ma, Ju ; Wang, Pengyuan ; Liu, Yucun ; Chen, Shanwen ; Guo, Shihao ; Ma, Yongchen ; Li, Tengyu ; Zhu, Jing

The activated form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], regulates numerous cellular processes, including inhibition of cancer progression. IL-1β has been reported to facilitate cancer development, especially by inducing an epithelial-to-mesenchymal transition (EMT) in several malignant tumors. However, the underlying mechanism of 1,25(OH)2D3 and IL-1β in colorectal cancer (CRC) still remains largely unknown. To fill in this knowledge gap, we measured cell proliferation and invasion by CCK-8 and Transwell assays after stimulation with 1,25(OH)2D3 and IL-1β. E-cadherin and vimentin were chosen as markers of EMT measured by immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blot. The expression and function of the vitamin D receptor (VDR) was evaluated by Western blot and luciferase reporter assay. qRT-PCR and RNA-FISH were performed to detect the expression and location of lncTCF7 in vitro. The binding sites of VDR in the lncTCF7 promoter were confirmed by a chromatin immunoprecipitation assay. Based on the above experiments, we found that 1,25(OH)2D3 attenuates IL-1β-induced increased proliferation and invasion in colorectal cancer through enhancing VDR, which inhibits the expression of lncTCF7 by directly binding to its promoter region.

01 Jul 2019·European review for medical and pharmacological sciences

LncRNA TCF7 triggered endoplasmic reticulum stress through a sponge action with miR-200c in patients with diabetic nephropathy.

Article

Author: Liu, H ; Sun, H-L

OBJECTIVETo investigate the functions and mechanisms of long non-coding RNA TCF7 (LncTCF7) in patients with diabetic nephropathy (DN).PATIENTS AND METHODSLncTCF7 and miR-200c expressions in DN (+) were detected by Real Time-Polymerase Chain Reaction (RT-PCR). In the established high-glucose group (HG) model, RT-PCR and Western blot were used to detect the expressions of lncTCF7 and key apoptotic genes. The effect of podocyte endoplasmic reticulum (ER) stress was detected in high glucose conditions after lncTCF7 siRNA transfection. The miR-200c level was detected in lncTCF7 overexpressing cell model and the luciferase reporter gene assay was performed to verify the potential binding site of lncTCF7 with miR-200c. Furthermore, ER stress-associated genes were detected in patients with DN. Finally, in the HG model, the levels of ER stress were detected by WB after transfection with miR-200c inhibitor and lncTCF7 siRNA with miR-200c mimics.RESULTSResults showed that the lncTCF7 expression was up-regulated, while miR-200c was significantly downregulated in patients with DN (+). In the HG model, the expression of lncTCF7 was significantly increased and some key ER stress-associated genes, such as CHOP, XBP1, and cleaved caspase3, were significantly increased, while the anti-apoptotic protein Bcl-2 was significantly decreased. However, after inhibiting the lncTCF7 expression, these gene levels were reversed. In lncTCF7 overexpressing cells, miR-200c expression was significantly down-regulated compared with the control (p<0.05) and the luciferase reporter gene assay results showed that lncTCF7 could directly bind to miR-200c. In the HG model, after inhibiting lncTCF7 expression, the miR-200c level was increased, while the ER stress-associated proteins CHOP, XBP1, and cleaved caspase3 were significantly repressed. However, these proteins were reversed after inhibiting miR-200c expression. In addition, the expressions of ER stress-associated protein and apoptotic protein in human DN patients were consistent with HG cell model.CONCLUSIONSLncRNA TCF7 triggered endoplasmic reticulum stress through a sponge action with miR-200c in patients with diabetic nephropathy.

News (Medical) associated with WSPAR

15 Jun 2023

·pipelinereview.com

AntlerA Norrin/Wnt-agonist ANT antibody enters clinical trials through a strategic partnership with EyeBio

SAN FRANCISCO, CA, USA I June 15, 2023 I AntlerA Norrin/Wnt-agonist antibody through a strategic partnership with EyeBio enters clinical trials for treatment of retinopathies. AntlerA previously reported the development of a Norrin/Wnt-mimetic for treatment of leaky blood vessels in the eye. “We are pleased to support EyeBio in the development and advancement of EYE103, a Norrin/Wnt-mimetic, into the clinic. Built based on AntlerA’s ANT-Pharm platform the tetravalent antibody molecule binds specifically to FZD4/LRP5 receptors leading to Wnt-signaling and restoration of blood vessels integrity in the eye.” said Dr. Sekar Seshagiri, CEO, AntlerA Therapeutics. He further added “This is a first-in class molecule for treatment of diabetic retinopathy and several pediatric retinal diseases such as FEVR/Norrie, Coats, and ROP” About AntlerA Therapeutics, Inc. AntlerA Therapeutics is a regenerative medicines company focused on developing novel protein therapeutics that function by modulating Wnt signaling to harness the regenerative potential of tissue resident stem cells. For more information, please visit www.antlera.com

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