3,4-Diaminopyridine may improve myasthenia gravis with M
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            SK antibodies

Evoli, Amelia; Alboini, Paolo Emilio; Damato, Valentina; Iorio, Raffaele

doi:10.1212/wnl.0000000000002466

Cited by 35 publications

(23 citation statements)

References 7 publications

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“…3,4‐DAP is used to treat the Lambert–Eaton myasthenic syndrome and congenital myasthenic syndromes (CMS). It has been tested, so far, in a few MuSK + MG patients, with mild‐to‐moderate clinical effects, and, in our experience, was remarkably well tolerated . Sympathomimetics, such as ephedrine and albuterol, proved very effective in CMS related to DOK7 and COLQ mutations, and, more recently, in patients with MUSK mutations .…”

Section: Therapymentioning

confidence: 74%

Myasthenia gravis with antibodies to MuSK: an update

Evoli

Alboini

Damato

et al. 2017

Annals of the New York Academy of Sciences

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113

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Myasthenia gravis with antibodies to the muscle-specific tyrosine kinase (MuSK MG) is a rare disease with distinctive pathogenic mechanisms and clinical features. An acute onset and predominant bulbar muscle weakness are very common and highly suggestive of the disease. On the other hand, a more indolent course, atypical ocular presentation, and signs of cholinergic hyperactivity may complicate the diagnosis. Though MuSK MG is still a severe disease, over the years we have observed a steady reduction in the rate of respiratory crisis and a significant improvement in the clinical outcome, both likely related to earlier diagnosis and timely treatment. Despite the improved management, MuSK MG patients tend to remain dependent on long-term immunosuppressive treatment and may develop permanent disabling weakness. In uncontrolled studies, B cell depletion with rituximab proved effective in most patients with refractory disease, inducing prolonged clinical responses associated with a sustained reduction of serum antibody levels. Promising results from experimental studies and case reports suggest that both 3,4-diaminopyridine and albuterol may be effective as symptomatic agents.

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Section: Therapymentioning

confidence: 74%

Myasthenia gravis with antibodies to MuSK: an update

Evoli

Alboini

Damato

et al. 2017

Annals of the New York Academy of Sciences

Self Cite

113

View full text Add to dashboard Cite

show abstract

“…Despite long-term immunosuppression, 13 patients remained affected with symmetrical ophthalmoparesis that was associated with permanent bulbar or neck weakness. All MG manifestations markedly improved in two of these cases treated with rituximab, while in a patient, who had refused immunosuppression, ophthalmoplegia was moderately improved by 3–4 DAP 7. Pyridostigmine partially relieved ptosis and diplopia in 7 of 10 patients; 3–4 DAP was effective on ptosis in 2 out of 3 patients.…”

Section: Resultsmentioning

confidence: 90%

Pattern of ocular involvement in myasthenia gravis with MuSK antibodies

Evoli

Alboini

Iorio

et al. 2017

J Neurol Neurosurg Psychiatry

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“…In the mouse active immunization model of MuSK MG, acute treatment of myasthenic muscles with 3,4‐DAP produced a similar improvement in endplate potential amplitudes . An initial case study reported that 3,4‐DAP may indeed be useful for treating MuSK MG patients …”

Section: Initial Testing Of Therapeutics In the Passive Igg Transfer mentioning

confidence: 89%

The mouse passive‐transfer model of MuSK myasthenia gravis: disrupted MuSK signaling causes synapse failure

Ghazanfari

Trajanovska

Morsch

et al. 2017

Annals of the New York Academy of Sciences

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While the majority of myasthenia gravis patients express antibodies targeting the acetylcholine receptor, the second most common cohort instead displays autoantibodies against muscle-specific kinase (MuSK). MuSK is a transmembrane tyrosine kinase found in the postsynaptic membrane of the neuromuscular junction. During development, MuSK serves as a signaling hub, coordinating the alignment of the pre- and postsynaptic components of the synapse. Adult mice that received repeated daily injections of IgG from anti-MuSK myasthenia gravis patients developed muscle weakness, associated with neuromuscular transmission failure. MuSK autoantibodies are predominantly of the IgG4 type. They suppress the kinase activity of MuSK and the phosphorylation of target proteins in the postsynaptic membrane. Loss of postsynaptic acetylcholine receptors is the primary cause of neuromuscular transmission failure. MuSK autoantibodies also disrupt the capacity of the motor nerve terminal to adaptively increase acetylcholine release in response to the reduced postsynaptic responsiveness to acetylcholine. The passive IgG transfer model of MuSK myasthenia gravis has been used to test candidate treatments. Pyridostigmine, a first-line cholinesterase inhibitor drug, exacerbated the disease process, while 3,4-diaminopyridine and albuterol were found to be beneficial in this mouse model.

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3,4-Diaminopyridine may improve myasthenia gravis with M u SK antibodies

Cited by 35 publications

References 7 publications

Myasthenia gravis with antibodies to MuSK: an update

Myasthenia gravis with antibodies to MuSK: an update

Pattern of ocular involvement in myasthenia gravis with MuSK antibodies

The mouse passive‐transfer model of MuSK myasthenia gravis: disrupted MuSK signaling causes synapse failure

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