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Last update 23 Jan 2025

RGMa

Last update 23 Jan 2025

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

285

Literatures (Medical) associated with RGMa

01 Feb 2025·The Journal of Pain

Genetics of constant and severe pain in the NAPS2 cohort of recurrent acute and chronic pancreatitis patients

Article

Author: Yadav, Dhiraj ; Albers, Kathryn M ; Whitcomb, David C ; Dunbar, Ellyn K ; Greer, Phil J ; Saloman, Jami L

Recurrent acute and chronic pancreatitis (RAP, CP) are complex, progressive inflammatory diseases with variable pain experiences impacting patient function and quality of life. The genetic variants and pain pathways in patients contributing to most severe pain experiences are unknown. We used previously genotyped individuals with RAP/CP from the North American Pancreatitis Study II (NAPS2) of European Ancestry for nested genome-wide associated study (GWAS) for pain-severity, chronicity, or both. Lead variants from GWAS were determined using FUMA. Loci with p<1e-5 were identified for post-hoc candidate identification. Transcriptome-wide association studies (TWAS) identified loci in cis and trans to the lead variants. Serum from phenotyped individuals with CP from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED) was assessed for BDNF levels using Meso Scale Discovery Immunoassay. We identified four pain systems defined by candidate genes: 1) Pancreas-associated injury/stress mitigation genes include: REG gene cluster, CTRC, NEURL3 and HSF22. 2) Neural development and axon guidance tracing genes include: SNPO, RGMA, MAML1 and DOK6 (part of the RET complex). 3) Genes linked to psychiatric stress disorders include TMEM65, RBFOX1, and ZNF385D. 4) Genes in the dorsal horn pain-modulating BDNF/neuropathic pathway included SYNPR, NTF3 and RBFOX1. In an independent cohort BDNF was significantly elevated in patients with constant-severe pain. Extension and expansion of this exploratory study may identify pathway- and mechanism-dependent targets for individualized pain treatments in CP patients. PERSPECTIVE: Pain is the most distressing and debilitating feature of chronic pancreatitis. Yet many patients with chronic pancreatitis have little or no pain. The North American Pancreatitis Study II (NAPS2) includes over 1250 pancreatitis patients of all progressive stages with all clinical and phenotypic characteristics carefully recorded. Pain did not correlate well with disease stage, inflammation, fibrosis or other features. Here we spit the patients into groups with the most severe pain and/or chronic pain syndromes and compared them genetically with patients reporting mild or minimal pain. Although some genetic variants associated with pain were expressed in cells (1) of the pancreas, most genetic variants were linked to genes expressed in the nervous system cells associated with (2) neural development and axon guidance (as needed for the descending inhibition pathway), (3) psychiatric stress disorders, and (4) cells regulating sensory nerves associated with BDNF and neuropathic pain. Similar and overlapping genetic variants in systems 2 -4 are also seen in pain syndromes form other organs. The implications for treating pancreatic pain are great in that we can no longer focus on just the pancreas. Furthermore, new treatments designed for pain disorders in other tissues may be effective in some patient with pain syndromes from the pancreas. Further research is needed to replicate and extend these observations so that new, genetics-guided rational treatments can be developed and delivered.

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 Jan 2025·Brain Research Bulletin

The role of H3K27 acetylation in oxygen-glucose deprivation-induced spinal cord injury and potential for neuroprotective therapies

Article

Author: Guan, Zheng ; Li, Weina ; Liu, Jingjie ; Wang, Heying ; Zhou, Ting ; Wang, Jing ; Gong, Yu

OBJECTIVESpinal cord injury (SCI) is a debilitating condition that often results in paralysis and lifelong medical challenges. Research has shown that epigenetic modifications, particularly histone acetylation, play a role in neuroprotection following hypoxic-ischemic events in SCI. The objective of this study was to explore the effects of histone H3K27 acetylation, along with its underlying mechanisms, on the tolerance to hypoxia and ischemia in SCI.METHODSThis study employed an organotypic spinal cord slice culture model subjected to oxygen-glucose deprivation (OGD). We assessed cell apoptosis and changes in cellular type patterns under these conditions. Following hypoxia and ischemia, we analyzed the expression and distribution of H3K27ac across various nerve cell types. To identify key downstream genes, we integrated ChIP-seq and RNA-seq analyses, investigating molecular mechanisms driving the response to OGD in this model.RESULTSOGD stimulation increased cell apoptosis and induced time-dependent changes in the expression patterns of neurons, astrocytes, microglia, and oligodendrocytes in organotypic spinal cord slices, accompanied by a significant reduction in H3K27ac levels. Integrated ChIP-seq and RNA-seq analyses revealed that H3K27ac downregulation under hypoxic and ischemic conditions contributes to spinal cord damage by promoting neuroinflammation and disrupting gene regulation. Furthermore, we identified key downstream targets, including Apoc1, Spp1, Aff1, Brd4, KCNN3, and Rgma, which may represent promising therapeutic targets for SCI.CONCLUSIONOur data underscore the pivotal role of H3K27ac in the organotypic spinal cord slice culture model following OGD exposure, offering promising avenues for neuroprotective therapies via epigenetic-immune regulation.

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RGMa

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