Myasthenia gravis: the changing treatment landscape in the era of molecular therapies

Iorio, Raffaele

doi:10.1038/s41582-023-00916-w

Cited by 23 publications

(6 citation statements)

References 162 publications

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“…Two common conditions in clinical practice that involve problems with the transmission of signals between nerves and muscles are MG and Lambert–Eaton myasthenic syndrome (LEMS) [ 21 , 66 , 67 ]. These disorders often involve defects in neuromuscular transmission.…”

Section: Nmj-related Disordersmentioning

confidence: 99%

“…These disorders often involve defects in neuromuscular transmission. MG is an autoimmune disorder in which muscle weakness occurs because of the impairment of the NMJ and neuromuscular transmission [ 21 , 68 , 69 ]. The most common symptoms are weakness of the eye muscles and of the muscles that control breathing and swallowing.…”

Section: Nmj-related Disordersmentioning

confidence: 99%

“…While the main function of the NMJ is the transmission of signals between the motor neuron and the skeletal muscle fiber to induce muscle contraction and movement, there are also positive and negative influences on the NMJ, as shown in Figure 2. Two common conditions in clinical practice that involve problems with the transmission of signals between nerves and muscles are MG and Lambert-Eaton myasthenic syndrome (LEMS) [21,66,67]. These disorders often involve defects in neuromuscular transmission.…”

Section: Nmj-related Disordersmentioning

confidence: 99%

“…Visualizing and analyzing the NMJ in rodent models of these disorders is crucial, particularly during the early stages of the disease. The NMJ is also involved in myasthenic disorders such as myasthenia gravis (MG) and is vulnerable to neurotoxins [ 21 , 22 , 23 ]. Additionally, it is known to degrade before axon loss occurs in response to axotomy and is a common feature of aging.…”

Section: Introductionmentioning

confidence: 99%

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Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases

Nemeth,

Banik,

Haque

2024

IJMS

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The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot–Marie–Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.

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Section: Nmj-related Disordersmentioning

confidence: 99%

Section: Nmj-related Disordersmentioning

confidence: 99%

Section: Nmj-related Disordersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases

Nemeth,

Banik,

Haque

2024

IJMS

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“…The goal of MG treatment is to achieve complete remission or minimal manifestation status with minimal side effects and eventually to avoid a myasthenic crisis [ 10 ]. Despite the availability of standard therapies, including acetylcholinesterase inhibitors, steroids, steroid-sparing immunosuppressants, and thymectomy, symptoms of MG are unsatisfactorily treated in up to half of individuals over the course of their disease [ 11 ].…”

Section: Introductionmentioning

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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Cancer Frequency in MuSK Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology

Falso,

Gessi,

Marini

et al. 2024

Annals of Neurology

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Cancer frequency in muscle‐specific kinase myasthenia gravis (MuSK‐MG) has not yet been explored and the mechanisms leading to the formation of MuSK IgG remain elusive. We aimed to explore cancer frequency in MuSK‐MG patients and to assess MuSK expression in cancer cells from 2 tumors occurred in this cohort. Immunohistochemistry on tumor specimens revealed the expression of MuSK in the cancer cells from primary mediastinal B cell lymphoma and endometrial carcinoma. Twenty‐one males and 73 females were enrolled. Fifteen cancers occurred in 13 of 94 patients (13.8%). Patients with cancer were significantly older at time of MuSK‐MG onset. ANN NEUROL 2024

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Myasthenia gravis: the changing treatment landscape in the era of molecular therapies

Cited by 23 publications

References 162 publications

Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases

Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases

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

Cancer Frequency in MuSK Myasthenia Gravis and Histological Evidence of Paraneoplastic Etiology

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