New and emerging treatments for myasthenia gravis

DeHart-McCoyle, Mckenzye; Patel, Shital; Du, Xinli

doi:10.1136/bmjmed-2022-000241

Cited by 9 publications

(3 citation statements)

References 19 publications

(23 reference statements)

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“…It is widely recognized that dysregulated complement activation is a primary pathogenic mechanism in MG. Notably, C5 inhibitors, such as Eculizumab, have proven effective in preventing complement-dependent membrane attacks at the neuromuscular junction, presenting a promising avenue for the treatment of MG [ 42 ]. Future research is warranted to investigate the potential therapeutic implications of CPN2 in MG.…”

Section: Discussionmentioning

confidence: 99%

Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis

Li,

Wang,

et al. 2024

J Transl Med

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Background Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. Methods By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. Results We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. Conclusions This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.

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Section: Discussionmentioning

confidence: 99%

Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis

Li,

Wang,

et al. 2024

J Transl Med

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“…According to recent evidence, patients with MG, particularly those with refractory disease, could be benefit from novel targeted treatments, including neonatal Fc receptor antagonists, complement inhibitors, B cell depletors, chimeric antigen receptor T cell immunotherapy, etc. These novel agents showed advantages over conventional immunosuppressive treatments, with faster onset of action and favorable safety profile [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Epidemiology, Patient Characteristics, and Treatment Patterns of Myasthenia Gravis in Taiwan: A Population-Based Study

Tsai,

Chien,

Hung

et al. 2024

Neurol Ther

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Introduction Myasthenia gravis (MG) is a chronic neuromuscular disease leading to significant disease burden. This study aimed to investigate the epidemiology of MG in Taiwan. Methods A retrospective study was conducted using the Taiwan National Health Insurance Research Database. Prevalent patients with MG diagnosis (either ocular or generalized MG) from 2013 to 2019 were identified, and 2813 patients with initial MG diagnosis from 2014 to 2019 were further defined as the incident cohort. Patient characteristics, treatment patterns, and the occurrence of MG-related events were analyzed. Results The number of prevalent patients with MG increased from 4476 in 2013 to 5752 in 2019, with the prevalence rate increasing from 19 to 24 per 100,000 population. The incidence rate also slightly increased from 1.9 to 2.3 per 100,000 population during the study period. Almost all incident patients (99%, n = 2791) received MG-related treatment during the follow-up period. Among 1876 patients who received monotherapy as their initial treatment in the outpatient setting, the mean time from the index date to initial treatment was 48.8 (standard deviation 164.3) days, and most patients received acetylcholinesterase inhibitors (88.5%, n = 1661) as their initial treatment. During the first year after the index date, 133 (4.7%) incident patients experienced their first myasthenic crisis, and 96.2% of these events occurred within 3 months. Conclusion The prevalence of MG increased steadily in Taiwan, and the treatment of patients with MG was consistent with guidelines. Despite a high treatment rate, patients still experienced MG-related events, highlighting the limitation of current treatments and emphasizing the need for early intervention and novel treatment approaches. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-024-00619-4.

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“…It does this by blocking the conversion of C5a to C5b. With regard to the potential efficacy of the proteasome inhibitor bortezomib, at least one case of a beneficial effect of this drug has been described in a patient with severe myasthenia gravis with anti-MuSK antibodies [ 102 , 103 ].…”

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 and emerging treatments for myasthenia gravis

Cited by 9 publications

References 19 publications

Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis

Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis

Epidemiology, Patient Characteristics, and Treatment Patterns of Myasthenia Gravis in Taiwan: A Population-Based Study

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

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