Last update 01 Nov 2024

RGMa

Last update 01 Nov 2024

Basic Info

Synonyms

Repulsive guidance molecule A, repulsive guidance molecule BMP co-receptor a, repulsive guidance molecule family member a

+ [4]

Introduction

Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8.

Drugs associated with RGMa

Unasnemab

Target

RGMa

Mechanism

RGMa inhibitors

Active Org.

Mitsubishi Tanabe Pharma America, Inc.Startup [+2]

Originator Org.

Osaka University

Active Indication

acute spinal cord injury [+3]

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Elezanumab

Target

RGMa

Mechanism

RGMa inhibitors [+2]

Active Org.

AbbVie, Inc.

Originator Org.

AbbVie, Inc.

Active Indication

Acute Ischemic Stroke [+1]

Inactive Indication

Multiple Sclerosis [+1]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with RGMa

NCT05396235 / CompletedPhase 1

A Clinical Pharmacology Study of MT-3921 in Healthy Adult Males

The purpose of this study is to investigate the safety, tolerability, and pharmacokinetics when MT-3921 or a placebo is intravenously given to Japanese healthy adult male subjects

Start Date03 Aug 2022

Sponsor / Collaborator

Mitsubishi Tanabe Pharma Corp.

NCT05240612 / CompletedPhase 1

A Clinical Pharmacological Study of MT-3921 in Subjects With Human T-cell Leukemia Virus Type 1 (HTLV-1)-Associated Myelopathy (HAM)

The purposes of this study is to assess the safety, tolerability, and pharmacokinetics of MT-3921 in subjects with Human T-cell Leukemia Virus Type 1 (HTLV-1)-Associated Myelopathy(HAM).
Subjects meeting eligibility criteria will enter the 6-month double-blind period. Subjects will be randomized in a 2:1 ratio to receive MT-3921 or placebo in a double blind manner.

Start Date02 May 2022

Sponsor / Collaborator

Mitsubishi Tanabe Pharma Corp.

NCT04683848 / Active, not recruitingPhase 2

A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of MT-3921 in Subjects With Acute Traumatic Cervical Spinal Cord Injury

The purpose of this study is to compare the efficacy and safety of intravenous (IV) infusions of MT-3921 to placebo in subjects with acute traumatic cervical spinal cord injury.
Subjects meeting eligibility criteria will enter the 6-month double-blind period. Subjects will be randomized in a 2:1 ratio to receive MT-3921 or placebo in a double blind manner.

Start Date27 Aug 2021

Sponsor / Collaborator

Mitsubishi Tanabe Pharma America, Inc.Startup

100 Clinical Results associated with RGMa

100 Translational Medicine associated with RGMa

0 Patents (Medical) associated with RGMa

276

Literatures (Medical) associated with RGMa

01 Jan 2025·Journal of Ethnopharmacology

Integrated lipidomic and transcriptomics to explore the effects of ethyl acetate extract of Herpetospermum pedunculosum on nonalcoholic fatty liver disease in mice

Article

Author: Tan, Rui ; Adiham, Akida ; Han, Cairong ; Zhang, Zhongrui ; Gong, Puyang ; Zhang, Boyu ; Gu, Jian

ETHNOPHARMACOLOGICAL RELEVANCEHerpetospermum pedunculosum (Ser.) C.B. Clarke (HP), a traditional Tibetan medicine used to treat hepatobiliary diseases, was confirmed that lignans-enriched ethyl acetate extract of HP (EAHP) could alleviate the hepatic injury by modern pharmacological evidence. However, the effects and potential mechanisms of EAHP against nonalcoholic fatty liver disease (NAFLD) are still unknown.AIM OF THE STUDYTo reveal the effects of EAHP on NAFLD and explore the potential mechanisms from the perspective of lipidomics and transcriptomics.MATERIALS AND METHODSUPLC‒Q-TOF‒MS analysis was carried out to investigate the chemical components of EAHP. A Choline-deficient, L-amino acid defined, high fat diet (CDAHFD) was used to establish a NAFLD mouse model. The anti-NAFLD effects of various dosages of EAHP were evaluated by biochemical indexes and histological analysis. Hepatic lipidomic and transcriptomic analysis and multiple bioinformatics methods were used to screen biomarkers and signaling pathways. The levels of the corresponding genes were verified by qPCR.RESULTS36 kinds of compounds were identified by UPLC‒Q-TOF‒MS analysis. Oral treatment with EAHP significantly decrease the liver index and the levels of ALT and AST in the serum. The measurements lipid content and Oil Red O staining results suggested that EAHP ameliorated lipid metabolism disorders by reducing the content of TG and LDL-C, increasing HDL-C in the liver. H&E staining and ELISA revealed that EAHP restored hepatic inflammatory infiltration and decrease the levels of IL-1β, IL-6, TNF-α, and increase IL-10 in the serum. Lipidomic analysis showed that EAHP could regulate CDAHFD-induced lipid metabolic disorder. The different lipid metabolites included TG, phosphatidyl choline (PC), diacylglycerol (DG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), ceramide (Cer). Transcriptomic analysis revealed that Bmp8b, Nbl1, Rgma, Sphk1, Thbs1, and Ugt8a were important regulators, which were associated with TGF-β signaling pathway and sphingolipid metabolism. The expressions of above genes detected by were qPCR consistent with transcriptomic data.CONCLUSIONSThe ameliorative effects of EAHP on NAFLD are potentially attributable to the regulation of sphingolipid metabolism and TGF-β signaling pathway, etc., which results in abnormal hepatic lipid metabolism and inflammatory response.

01 Sep 2024·Neurotherapeutics

Long non-coding RNA SNHG12 regulates leptomeningeal collateral remodeling via RGMa after ischemic stroke

Article

Author: Wang, Zijie ; Jiang, Anan ; Zhang, Shaoru ; Wu, Qisi ; Qin, Xinyue ; Cheng, Ruiqi

Leptomeningeal anastomoses or pial collateral arteries are crucial for restoring cerebral blood flow (CBF) after an ischemic stroke. Vascular smooth muscle cells (VSMCs) are hypothesized to regulate the extent of this adaptive response, while the specific molecular mechanisms underlying this process are still being investigated. SNHG12, a long non-coding RNA, has been shown to influence several diseases related angiogenesis, including osteosarcoma and gastric cancer. However, the role of SNHG12 in contractile VSMC dedifferentiation during collateral arteriogenesis-related strokes remains unclear. Here we demonstrated that SNHG12 is a positive regulator of MMP9 and VSMC dedifferentiation, which enhances pial collateral arteriogenesis following cerebrovascular occlusion. Pial collateral remodeling is limited by the crosstalk between SNHG12-MMP9 signaling in VSMCs, which is mediated through repulsive guidance molecule a (RGMa) regulation. Thus, targeting SNHG12 may represent a therapeutic strategy for improving collateral function, neural tissue health, and functional recovery following ischemic stroke.

06 Aug 2024·Microbiology Spectrum

Anti-biofilm activities and antibiotic synergy of naturally occurring compounds against drug-resistant rapidly growing mycobacteria

Article

Author: Hsu, Chun-Ru ; Huang, Yu-Chieh ; Yen, Chun-Lun ; Huang, Ya-Ling ; Huang, Chen-Hsiu

ABSTRACT Some naturally occurring compounds, known for their antimicrobial activities, have been employed as food additives. However, their efficacy in treating infections caused by antibiotic-resistant bacteria is yet to be fully explored. Rapidly growing mycobacteria (RGM), a category within nontuberculous mycobacteria (NTM), are prevalent in various environments and can lead to infections in humans. The rise of antimicrobial resistance within RGM is a documented concern. In this study, we reported that four specific natural compounds effectively inhibited the growth and biofilm formation of three key RGM pathogens M. abscessus , M. fortuitum , and M. chelonae . We screened 12 natural compounds for their effectiveness against antibiotic-resistant clinical strains of RGM. Four compounds showed significant inhibitory effects from the most effective to least: trans -cinnamaldehyde, carvacrol, gentisaldehyde, and phloroglucinaldehyde. In the analysis of time-killing kinetics, gentisaldehyde and phloroglucinaldehyde displayed bactericidal activity while trans -cinnamaldehyde and carvacrol exhibited bacteriostatic effects. At 1× minimal inhibition concentrations, these compounds significantly reduced biofilm formation in all three RGM species to levels between 2.9% and 20.5% relative to controls. Checkerboard assays indicated synergistic interactions between these four compounds and antibiotics such as amikacin, clarithromycin, and linezolid. Of these 12 compound-antibiotic combinations, the pairs of carvacrol-linezolid, carvacrol-amikacin, and gentisaldehyde-clarithromycin demonstrated the most synergy against multiple RGM strains. Moreover, two other compounds citral and geraniol showed synergism with all three test antibiotics. Time-killing assays further confirmed most of synergistic combinations identified in the checkerboard tests. Our research suggests the potential of these essential oils and phenolic aldehydes, both individually and in combination with antibiotics, in treating RGM infections. In addition, this work illuminates applications of these natural compounds in environmental remediation to mitigate bacterial persistence for the control of infectious diseases. IMPORTANCE The emergence of antimicrobial resistance within rapidly growing mycobacteria (RGM) poses a significant threat to public health. This study investigates the potential of naturally occurring compounds to combat infections caused by antibiotic-resistant RGM including M. abscessus , M. fortuitum , and M. chelonae . We identified four specific natural compounds showing impressive inhibitory effects against antibiotic-resistant clinical strains. These compounds not only inhibited the growth and biofilm formation but also exhibited synergistic interactions with antibiotics against key RGM pathogens. Our findings highlight the alternative treatment strategies for RGM infections and potential environmental applications of these natural compounds in mitigating microbial persistence and controlling infectious diseases.

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