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Last update 08 May 2025

RGMa

Last update 08 May 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 Corp. [+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

/ CompletedPhase 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.

100 Clinical Results associated with RGMa

100 Translational Medicine associated with RGMa

0 Patents (Medical) associated with RGMa

284

Literatures (Medical) associated with RGMa

01 Jun 2025·North American Spine Society Journal (NASSJ)

Traumatic spinal cord injury: a review of the current state of art and future directions – what do we know and where are we going?

Article

Author: Johnston, Benjamin R ; Izzy, Saef ; Mensah, Emmanuel O ; He, Zhigang ; Parker, Tariq ; Lu, Yi ; Chalif, Eric ; Fehlings, Michael G ; Saigal, Rajiv ; Chalif, Joshua I

BackgroundTraumatic spinal cord injury (SCI) remains a devastating condition, with limited functional recovery despite advancements in clinical management and understanding of its mechanisms. SCI pathophysiology involves primary mechanical trauma and secondary neuroimmune and structural changes, leading to neuronal death and chronic functional deficits.MethodsThrough a comprehensive literature review of articles published in the PubMed, MEDLINE, Embase, and Cochrane Reviews Library databases, this article provides an update on the current management of traumatic SCI with a focus on these emerging therapeutic strategies that hold potential for future advancements in the field.ResultsCurrent management strategies include pre-hospital care, acute clinical interventions, surgical decompression and spine destabilization, and neurorehabilitation. Despite these interventions, SCI patients often fail to fully restore lost functions. Emerging therapies focus on neuroprotection, neuroregeneration, and neuromodulation, leveraging advances in molecular biomarkers, imaging techniques, and cell-based treatments. Neuroprotective agents, including the sodium-glutamate antagonist riluzole, aim to keep cells alive through the secondary injury phase, while regenerative strategies utilize neurotrophic factors and stem cell transplantation or approaches to target inhibitor molecules such as NOGO or RGMa to regenerate new cells, axons, and neural circuits. Neuromodulation techniques, such as electrical and magnetic field stimulation, offer promising avenues for functional recovery. Combining these novel therapies with traditional neurorehabilitation holds potential for improved outcomes.ConclusionsWhile significant strides have been made in understanding the mechanisms underlying SCI and in developing novel therapeutic approaches, the challenge and opportunity will be to tailor treatments to fit the heterogenous clinical presentation of patients with SCI and to better understand the heterogeneity in clinical trajectories.

01 Mar 2025·Neurotherapeutics

Anti-RGMa neutralizing antibody ameliorates vascular cognitive impairment in mice

Article

Author: Yamamoto, Masaya ; Uno, Hiroki ; Yamashita, Toshihide ; Maki, Takakuni ; Itokazu, Takahide ; Shibuya, Nao

Repulsive Guidance Molecule A (RGMa) is well-recognized for its role in axon guidance. Recent studies have unveiled its diverse functions under pathological conditions within the central nervous system, such as spinal cord injury, multiple sclerosis, and Parkinson's disease. In this study, we explored the involvement of RGMa and the therapeutic effects of an anti-RGMa neutralizing antibody in a mouse model of vascular dementia (VaD). The VaD mouse model was established using the bilateral common carotid artery stenosis (BCAS) method. Immunohistochemical analysis revealed that these mice exhibited increased RGMa expression in the hippocampus, which coincided with reduced neurogenesis and impaired cholinergic innervation. These alterations manifested as cognitive impairments in the BCAS mice. Significantly, treatment with anti-RGMa neutralizing antibody reversed these pathological changes and cognitive deficits. Our findings suggest that RGMa plays a pivotal role in VaD pathology within the hippocampus and propose the anti-RGMa antibody as a promising therapeutic avenue for treating VaD.

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.

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