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Last update 08 May 2025

GFRA4

Last update 08 May 2025

Basic Info

Synonyms

GDNF family receptor alpha 4, GDNF family receptor alpha-4, GDNF receptor alpha-4

+ [4]

Introduction

Receptor for persephin (PSPN), a growth factor that exhibits neurotrophic activity on mesencephalic dopaminergic and motor neurons (PubMed:11116144). Acts by binding to its coreceptor, GFRA4, leading to autophosphorylation and activation of the RET receptor (PubMed:11116144). May be important in C-cell development and, in the postnatal development of the adrenal medulla (PubMed:11116144).

Drugs associated with GFRA4

Anti-GFRA4 CAR-T (University of Pennsylvania)

Target

GFRA4

Mechanism

GFRA4 inhibitors

Active Org.

University of Pennsylvania

Originator Org.

University of Pennsylvania

Active Indication

Thyroid Cancer, Medullary

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

GFRalpha4 CAR-T(Tmunity Therapeutics)

Target

GFRA4

Mechanism

GFRA4 modulators

Active Org.

Tmunity Therapeutics, Inc.

Originator Org.

Tmunity Therapeutics, Inc.

Active Indication

Thyroid Cancer, Medullary

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with GFRA4

NCT04877613

/ Active, not recruitingPhase 1IIT

Phase I Trial of GFRα4 CAR T Cells in Adult Patients With Recurrent or Metastatic Medullary Thyroid Cancer

This is an open-label phase 1 study to assess the safety and feasibility of autologous T cells expressing a single-chain scFv targeting GFRα4 with tandem TCR/CD3ζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-GFRa4 cells") in patients with incurable medullary thyroid cancer (MTC).

Start Date19 Aug 2021

Sponsor / Collaborator

University of Pennsylvania

100 Clinical Results associated with GFRA4

100 Translational Medicine associated with GFRA4

0 Patents (Medical) associated with GFRA4

336

Literatures (Medical) associated with GFRA4

01 Jan 2023·Frontiers in oncology

ImmuneScore of eight-gene signature predicts prognosis and survival in patients with endometrial cancer.

Article

Author: Ma, Xiaoxin ; Wang, B O ; Gu, Jiahui ; Wang, Zihao

BackgroundEndometrial cancer (EC) is a common gynecological cancer worldwide and the sixth most common female malignant tumor. A large number of studies conducted through database mining have identified many biomarkers that may be related to survival and prognosis. However, the predictive ability of single-gene biomarkers is not sufficiently accurate. In recent years, tumors have been shown to interact closely with their microenvironment, and tumor-infiltrating immune cells in the tumor microenvironment were associated with therapeutic effects. Furthermore, sequencing technology has evolved and allowed the identification of genetic signatures that may improve prediction results. The purpose of this research was to discover the Cancer Genome Atlas (TCGA) data to evaluate new genetic features that can predict the prognosis of EC.MethodsmRNA expression profiling was analyzed in patients with EC identified in the TCGA database (n = 530). Differentially expressed genes at different stages of EC were screened using the immune cell enrichment score (ImmuneScore). Univariate and multivariate Cox regression analyses was applied to evaluate genes significantly related to overall survival and establish the prognostic risk parameter formula. Kaplan-Meier survival curves and the logarithmic rank method were applied to verify the importance of risk parameters for the prognostic forecast. The accuracy of survival prediction was confirmed using the nomogram and Receiver Operating Characteristic (ROC) curve analysis. The mRNA expression of eight genes were measured by qRT-PCR. According to COX and HR values, NBAT1, a representative gene among 8 genes, was selected for CCK-8 assay, colony formation assay and transwell invasion assay to verify the effect on survival.ResultsEight related genes (NBAT1, GFRA4, PTPRT, DLX4, RANBP3L, UNQ6494, KLRB1, and PRAC1) were discovered to be significantly associated with the overall survival rate. According to these eight-gene signatures, 530 patients with EC were assigned to high- and low-risk subgroups. The prognostic capability of the eight-gene signature was not influenced by other elements.ConclusionsEight related gene markers were identified using ImmuneScore, which could predict prognosis and survival in patients with EC. These findings provide a basis for understanding the application of biological information in tumors and identifying the poor prognosis of EC.

01 Oct 2021·Journal of Chemical NeuroanatomyQ4 · MEDICINE

Hippocampal asymmetry and regional dispersal of nAChRs alpha4 and alpha7 subtypes in the adult rat

Q4 · MEDICINE

Article

Author: Rahimian, Neda ; Delavar, Amir ; Abbasi, Yusef ; Baradaran, Raheleh ; Anbarkeh, Fatemeh Rahimi ; Jaberi, Najmeh ; Khorasgani, Elham Moghtadaei

To better comprehend the relationship between left/right (L/R) differences and hippocampus functions is necessary knowledge of lateral asymmetry and regional distribution. This research was design to examine hippocampal L/R asymmetry and regional distribution profile of the alpha7 and alpha4 subtypes of nicotinic acetylcholine receptors (nAChRs) in the adult rat. 10-12-week-old twenty-four male wistar rats were randomly selected. After removing the brains, immunohistochemistry, real-time PCR, and western blot methods were applied to distinguish the presence of the receptors in the hippocampus. Outcomes stated that the mentioned receptors expression profile was spatial-dependent. As, the hippocampal dispersal of alpha7 and alpha4 subtypes in the left hippocampus (LH) was remarkably maximum compare with the right hippocampus (RH) (p = 0.001, p = 0.005 respectively). Furthermore, the alpha7 optical density (OD) was not significantly different in the diverse regions in hippocampus of adult rat (p = 0.057), while the maximum OD of the alpha4 was detected in the hippocampal dentate gyrus and CA3 regions of LH (p = 0.007, p = 0.009 respectively) and the minimum OD was in the CA1 of the RH (p = 0.019). In real time PCR evaluation, there is a significantly higher expression of alpha7 and alpha4 in LH compared to RH (p = 0.043, p = 0.049 respectively), also, for western blot (p = 0.042, p = 0.030 respectively). According to present data, the alpha7 and alpha4 nAChR subtypes expression profile demonstrated lateral asymmetry, the uniform regional dispersal for alpha7 and different regional dispersal for alpha4 in the adult rat hippocampus.

01 May 2021·Molecular and Cellular BiochemistryQ3 · BIOLOGY

MiR-195-5p inhibits proliferation and invasion of nerve cells in Hirschsprung disease by targeting GFRA4

Q3 · BIOLOGY

Article

Author: Wang, Gang ; Wu, Xiangyu ; Wang, Hefeng ; Guo, Feng ; Liu, Yang ; Zhang, Lijuan

Studies have reported that miR-195-5p plays a role in the Hirschsprung disease (HSCR). Our previous work found GDNF family receptor alpha 4 (GFRA4) is also associated with HSCR. In this study, we focused on whether miR-195-5p induces the absence of enteric neurons and enteric neural crest in HSCR by regulating GFRA4. The expression levels of GFRA4 and miR-195-5p in colon tissues were evaluated by real-time PCR (RT-PCR) assay. We overexpressed GFRA4 or miR-195-5p in SH-SY5Y cells, the cell proliferation, cell cycle, apoptosis and invasion were subsequently investigated by CCK-8 assay, EdU staining, Flow cytometry analysis and Transwell assay, respectively. We also established the xenograft model to detect the effect of miR-195-5p on tumor growth and GFRA4 and p-RET expressions. GFRA4 expression was significantly downregulated in the HSCR colon tissues when compared with that in the control tissues. Overexpression of GFRA4 significantly promoted proliferation, invasion and cell cycle arrest, and inhibited apoptosis of SH-SY5Y cells. We also proved that GFRA4 is a direct target of miR-195-5p, and miR-195-5p inhibited proliferation, invasion, cell cycle arrest and differentiation, and accelerated apoptosis in SH-SY5Y cells which can be reversed by GFRA4 overexpression. Furthermore, we demonstrated that miR-195-5p suppressed tumor growth, and observably decreased GFRA4 and p-RET expressions. Our findings suggest that miR-195-5p plays an important role in the pathogenesis of HSCR. MiR-195-5p inhibited proliferation, invasion and cell cycle arrest, and accelerated apoptosis of nerve cells by targeting GFRA4.

News (Medical) associated with GFRA4

07 Feb 2025

·www.pharmaceutical-technology.com

Relmada acquires Tourette’s therapy rights from Asarina

The therapy has shown potential in improving the symptoms of Tourette’s syndrome in a Phase IIa study. Credit: Jack_the_sparow/Shutterstock. Relmada Therapeutics has acquired complete worldwide ownership rights to Sepranolone from Sweden-based Asarina Pharma. Sepranolone is a neurosteroid being developed as a potential treatment for Tourette’s syndrome (TS) and other compulsive disorders. TS is a complex neurological condition characterised by involuntary tics. The asset purchase agreement between the two companies is valued at €3m ($3.12m). The therapy has demonstrated a favourable safety profile in clinical neuro/hormonal trials with more than 335 subjects. Relmada Therapeutics CEO Sergio Traversa stated: “We are very pleased to announce this agreement with Asarina. Sepranolone aligns with our company’s mission to find solutions for difficult-to-treat central nervous system (CNS) disorders. There is a serious unmet need for improved TS therapies – not only [in] reducing tics but also improving quality of life without serious side effects. “We have been impressed by the encouraging Phase IIa efficacy signal with clinically meaningful tic reductions and quality-of-life improvements, combined with a robust safety data package showing no CNS off-target effects, that we believe reflect the compound’s selective binding properties.” As a first-in-class GABAA-modulating steroid antagonist (GAMSA), Sepranolone works by normalising the activity of the GABAA receptor by targeting alpha-2 and alpha-4, the receptor subtypes. This mechanism avoids direct interference with GABAA signalling, offering a selective treatment approach for TS and associated disorders. The therapy is under the protection of several issued patents extended until 2038. The therapy has shown potential in improving TS symptoms in an open-label Phase IIa study compared to standard of care alone. The changes were measured by the Yale Global Tic Severity Scale (YGTSS) scoring system, compared to the baseline. In August 2022, the US Food and Drug Administration granted fast-track status to Relmada’s REL-1017 as a single agent for treating major depressive disorder.

Phase 2Clinical ResultFast TrackLicense out/in

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GFRA4

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