New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies

Sánchez-Tejerina, Daniel; Sotoca, Javier; Llauradó, Arnau; López-Diego, Veronica; Juntas-Moralès, Raul; Salvadó, María

doi:10.3390/jcm11216394

Cited by 12 publications

(9 citation statements)

References 112 publications

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“…Plasma cells are characterized by highly active immunoglobulin synthesis and, in these cells, accumulation of misfolded proteins and apoptosis resulting from the inhibition of the proteasome function [ 60 ]. In B-cell neoplasms, this strategy has been proven to be effective as a treatment, and the proteasome inhibitor Bortezomib has been studied for MG as it depletes both short- and long-lived plasma cells [ 68 , 69 ].…”

Section: Resultsmentioning

confidence: 99%

Delving into Molecular Pathways: Analyzing the Mechanisms of Action of Monoclonal Antibodies Integrated in IMGT/mAb-DB for Myasthenia Gravis

Golfinopoulou,

Giudicelli,

Manso

et al. 2023

Vaccines

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Background: Myasthenia Gravis (MG) is a rare autoimmune disease presenting with auto-antibodies that affect the neuromuscular junction. In addition to symptomatic treatment options, novel therapeutics include monoclonal antibodies (mAbs). IMGT®, the international ImMunoGeneTics information system®, extends the characterization of therapeutic antibodies with a systematic description of their mechanisms of action (MOA) and makes them available through its database for mAbs and fusion proteins, IMGT/mAb-DB. Methods: Using available literature data combined with amino acid sequence analyses from mAbs managed in IMGT/2Dstructure-DB, the IMGT® protein database, biocuration allowed us to define in a standardized way descriptions of MOAs of mAbs that target molecules towards MG treatment. Results: New therapeutic targets include FcRn and molecules such as CD38, CD40, CD19, MS4A1, and interleukin-6 receptor. A standardized graphical representation of the MOAs of selected mAbs was created and integrated within IMGT/mAb-DB. The main mechanisms involved in these mAbs are either blocking or neutralizing. Therapies directed to B cell depletion and plasma cells have a blocking MOA with an immunosuppressant effect along with Fc-effector function (MS4A1, CD38) or FcγRIIb engager effect (CD19). Monoclonal antibodies targeting the complement also have a blocking MOA with a complement inhibitor effect, and treatments targeting T cells have a blocking MOA with an immunosuppressant effect (CD40) and Fc-effector function (IL6R). On the other hand, FcRn antagonists present a neutralizing MOA with an FcRn inhibitor effect. Conclusion: The MOA of each new mAb needs to be considered in association with the immunopathogenesis of each of the subtypes of MG in order to integrate the new mAbs as a viable and safe option in the therapy decision process. In IMGT/mAb-DB, mAbs for MG are characterized by their sequence, domains, and chains, and their MOA is described.

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Section: Resultsmentioning

confidence: 99%

Delving into Molecular Pathways: Analyzing the Mechanisms of Action of Monoclonal Antibodies Integrated in IMGT/mAb-DB for Myasthenia Gravis

Golfinopoulou,

Giudicelli,

Manso

et al. 2023

Vaccines

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“…Several other narrative reviews also provide an overview of emerging novel therapies for gMG/MG [17,27,[57][58][59][60].…”

Section: Discussionmentioning

confidence: 99%

“…Ongoing and recently completed trials are evaluating various immunotherapies in MG including (i) the complement inhibitor zilucoplan; (ii) the FcRn inhibitors batoclimab, nipocalimab, and rozanolixizumab; (iii) the B‐cell inhibitors belimumab, inebilizumab, mezagitamab, and satralizumab; (iv) T‐cell inhibitors (chimeric autoantibody receptor T‐cell therapy and chimeric antigen receptor T‐cell therapy); and (v) hematopoietic stem cell transplantation (Table 2). Several other narrative reviews also provide an overview of emerging novel therapies for gMG/MG [17, 27, 57–60].…”

Section: Discussionmentioning

confidence: 99%

Refocusing generalized myasthenia gravis: Patient burden, disease profiles, and the role of evolving therapy

Saccà,

Salort‐Campana,

Jacob

et al. 2023

Euro J of Neurology

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Background and purposeGeneralized myasthenia gravis (gMG) continues to present significant challenges for clinical management due to an unpredictable disease course, frequent disease fluctuations, and varying response to therapy. The recent availability of new pharmacologic therapies presents a valuable opportunity to reevaluate how this disease is classified, assessed, and managed and identify new ways to improve the clinical care of patients with gMG.MethodsNarrative review was made of publications identified via searches of PubMed and selected congresses (January 2000–September 2022).ResultsNew consensus definitions are required to ensure consistency, to better characterize patients, and to identify patients who will benefit from specific drugs and earlier use of these agents. There is a need for more frequent, standardized patient assessment to identify the cause of motor function deficits, provide a clearer picture of the disease burden and its impact on daily living and quality of life (QoL), and better support treatment decision‐making. Novel approaches that target different components of the immune system will play a role in more precise treatment of patients with gMG, alongside the development of new algorithms to guide individualized patient management.ConclusionsgMG has a physical, mental, and social impact, resulting in a considerable burden of disease and substantially decreased QoL, despite standard treatments. The availability of novel, targeted treatments that influence key pathological mediators of gMG, together with new biomarkers, offers the potential to optimize patient management and ultimately enables a greater number of patients to achieve minimal manifestation status and a reduced burden of disease.

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“…Other antibodies targeting B lymphocytes (CD20, CD19) with potential relevance in myasthenia gravis, but without documented efficiency, include ocrelizumab, ofatumumab, obinutuzumab, ublituximab, and ibalizumab. In addition, the potential efficacy of the proteasome inhibitor was described in a report on the favorable impact of this drug in a patient with severe myasthenia gravis with anti-MuSK antibodies [ 88 , 89 , 90 , 91 , 92 ].…”

Section: Treatmentmentioning

confidence: 99%

MuSK Myasthenia Gravis—Potential Pathomechanisms and Treatment Directed against Specific Targets

Dziadkowiak,

Baczyńska,

Waliszewska-Prosół

2024

Cells

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Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies target structures within the neuromuscular junction, affecting neuromuscular transmission. Muscle-specific tyrosine kinase receptor-associated MG (MuSK-MG) is a rare, often more severe, subtype of the disease with different pathogenesis and specific clinical features. It is characterized by a more severe clinical course, more frequent complications, and often inadequate response to treatment. Here, we review the current state of knowledge about potential pathomechanisms of the MuSK-MG and their therapeutic implications as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of myasthenia gravis.

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New Targeted Agents in Myasthenia Gravis and Future Therapeutic Strategies

Cited by 12 publications

References 112 publications

Delving into Molecular Pathways: Analyzing the Mechanisms of Action of Monoclonal Antibodies Integrated in IMGT/mAb-DB for Myasthenia Gravis

Delving into Molecular Pathways: Analyzing the Mechanisms of Action of Monoclonal Antibodies Integrated in IMGT/mAb-DB for Myasthenia Gravis

Refocusing generalized myasthenia gravis: Patient burden, disease profiles, and the role of evolving therapy

MuSK Myasthenia Gravis—Potential Pathomechanisms and Treatment Directed against Specific Targets

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