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Myasthenia gravis

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:651
Name:Myasthenia gravis
Associated with:1 target
4 immuno-relevant ligands
Description
Myasthenia gravis is an autoimmune disease caused by auto-antibody attack on nicotinic acetylcholine receptors at the neuro-muscular junction. This disrupts nerve-muscle communication and results in muscle weakness and fatigue. Treatment has historically been limited to nonselective, chronic immunosuppressive therapies which have long-term toxicities. More selective and targeted therapies are now being developed, including the monoclonal antibody eculizumab (approved) and an investigational CAR-T cell therapy that targets antibody-producing plasma cells (Descartes-08; Cartesian Therapeutics; Phase 1/2).
Database Links
Disease Ontology: DOID:437
OMIM: 254200
Orphanet: ORPHA589

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols
nicotinic acetylcholine receptor α1 subunit
Role:  Target for autoantibodies
References:  4

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
efgartigimod alfa 1
Immuno Disease Comments: Phase 2 clinical trial NCT02965573 in MG patients has been completed. FDA orphan drug for MG (granted Sept 2017)
Clinical Use: The reference version of efgartigimod (efgartigimod alfa-fcab; ARGX-113) was advanced to clinical evaluations in patients with myasthenia gravis (MG), pemphigus vulgaris and primary immune thrombocytopenia. Click here to view ClinicalTrials.gov's registered ARGX-113 trials. ARGX-113 was granted FDA orphan drug designation for the treatment of MG in September 2017 [1]. In December 2021 the US FDA approved efgartigimod alfa-fcab (Vyvgart®) as a treatment for MG. EMA authorisation for Vyvgart® was issued in 2022. | View clinical data
rozanolixizumab
Immuno Disease Comments: Phase 2 clinical candidate for myasthenia gravis- see NCT03052751
Clinical Use: Rozanolixizumab (as research code UCB7665) was progressed into clinical trial in patients with myasthenia gravis and primary immune thrombocytopenia. EMA orphan designation as a treatment for myasthenia gravis has been in place since 2019.
First FDA approval was granted in June 2023, with rozanolixizumab authorised to treat patients with generalized myasthenia gravis who are positive for anti-acetylcholine receptor or anti-muscle-specific tyrosine kinase antibodies [3]. | View clinical data
CFZ533
Immuno Disease Comments: Phase 2 clinical candidate for moderate to severe Myasthenia gravis- see NCT02565576
Clinical Use: CFZ533 is being evaluated in clinical trials as a therapy for some autoimmune conditions and for preventing/reducing solid organ transplant rejection. Click here to link to ClinicalTrials.gov's full list of CFZ533 trials. | View clinical data
Bioactivity Comments: CFZ533 (mAb1) shows no agonist activity in an in vitro assay using isolated human PBMCs, blocks -mediated PBMC proliferation (IC50 58 ng/ml), inhibits CD40L-mediated TNF-α release from human monocyte derived dendritic cells (IC50 40 ng/ml), and has ADCC activity of < 1% (measuring specific lysis) [2]. | View biological activity
eculizumab
Immuno Disease Comments: Approved to treat generalized myasthenia gravis in patients with anti-acetylcholine receptor autoantibodies (granted in 2017 by FDA)
Clinical Use: Used to treat paroxysmal nocturnal hemoglobinuria (PNH). In the UK, NICE (National Institute for Health and Care Excellence) has approved eculizumab as a treatment for the rare, but fatal blood disorder, atypical haemolytic uraemic syndrome (aHUS). This decision was reached because eculizumab represents a significant innovation for a disease with a high unmet clinical need. Eculizumab treatment is expected to increase life expectancy of aHUS patients by decades. The FDA expanded approval in October 2017, to include treatment of patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody-positive.

SARS-C0V-2 and COVID-19: Eculizumab has been entered into clinical trials that aim to determine its ability to combat the dysregulated immune response that drives organ damage (lung and other organs) in patients with severe COVID-19. | View clinical data
Bioactivity Comments: Eculizumab binds to and blocks the cleavage of the complement protein C5, thereby preventing the formation of . The terminal half-life of eculizumab is 11.3 ± 3.4 days [5]. | View biological activity

References

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1. FDA. human anti-neonatal Fc receptor IgG1 Fc fragment. Accessed on 25/01/2018. Modified on 25/01/2018. www.accessdata.fda.gov, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=527316

2. Heusser C, Rush J, Vincent K. (2012) Silent fc variants of anti-cd40 antibodies. Patent number: WO2012065950. Assignee: Novartis Ag. Priority date: 15/11/2010. Publication date: 24/05/2012.

3. Hoy SM. (2023) Rozanolixizumab: First Approval. Drugs, 83 (14): 1341-1347. [PMID:37656420]

4. Lindstrom JM. (2000) Acetylcholine receptors and myasthenia. Muscle Nerve, 23 (4): 453-77. [PMID:10716755]

5. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. (2007) Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol, 25 (11): 1256-64. [PMID:17989688]