Becker myotonia-a recently identified mutation in iberian descendants with apparent acetazolamide-responsive phenotype

Moreira, Sandra; Barreto, Rui; Roriz, José Mário

doi:10.1002/mus.24534

Cited by 4 publications

(3 citation statements)

References 8 publications

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“…Besides sodium channel blockers, ACZ was reported to be efficient in small cohorts of MC patients [ 251 , 252 ] and could be considered a second choice. The mechanism of ACZ is not well defined, but it might stimulate the ClC-1 channel activity through intracellular acidification [ 39 , 253 ].…”

Section: Chloride Channel-related Muscle Disordersmentioning

confidence: 99%

Ion Channel Gene Mutations Causing Skeletal Muscle Disorders: Pathomechanisms and Opportunities for Therapy

Maggi

Bonanno

Altamura

et al. 2021

Cells

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Skeletal muscle ion channelopathies (SMICs) are a large heterogeneous group of rare genetic disorders caused by mutations in genes encoding ion channel subunits in the skeletal muscle mainly characterized by myotonia or periodic paralysis, potentially resulting in long-term disabilities. However, with the development of new molecular technologies, new genes and new phenotypes, including progressive myopathies, have been recently discovered, markedly increasing the complexity in the field. In this regard, new advances in SMICs show a less conventional role of ion channels in muscle cell division, proliferation, differentiation, and survival. Hence, SMICs represent an expanding and exciting field. Here, we review current knowledge of SMICs, with a description of their clinical phenotypes, cellular and molecular pathomechanisms, and available treatments.

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Section: Chloride Channel-related Muscle Disordersmentioning

confidence: 99%

Ion Channel Gene Mutations Causing Skeletal Muscle Disorders: Pathomechanisms and Opportunities for Therapy

Maggi

Bonanno

Altamura

et al. 2021

Cells

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“…Besides sodium channel blockers, the carbonic anhydrase inhibitor acetazolamide has been reported efficient in small cohorts of myotonic patients with sodium or chloride channel mutations [31,53,[89][90][91]. A number of non-responders have been also reported (Table 2).…”

Section: O R R E C T E D P R O O Fmentioning

confidence: 99%

Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine

Desaphy

Altamura

Vicart

et al. 2021

JND

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Background: Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital myopathies. The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of attacks in PP. Objective: This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background. Methods: We searched databases for randomized clinical trials (RCT) and other human studies reporting pharmacological treatments. Preclinical studies were considered to gain further information regarding mutation-dependent drug effects. All steps were performed by two independent investigators, while two others critically reviewed the entire process. Results: For NMD, RCT showed therapeutic benefits of mexiletine and lamotrigine, while other human studies suggest some efficacy of various sodium channel blockers and of the carbonic anhydrase inhibitor (CAI) acetazolamide. Preclinical studies suggest that mutations may alter sensitivity of the channel to sodium channel blockers in vitro, which has been translated to humans in some cases. For hyperkalemic and hypokalemic PP, RCT showed efficacy of the CAI dichlorphenamide in preventing paralysis. However, hypokalemic PP patients carrying sodium channel mutations may have fewer benefits from DCP compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies. Conclusions: These studies provided limited information about the response to treatments of individual mutations or groups of mutations. A major effort is needed to perform human studies for designing a mutation-driven precision medicine in muscle ion channelopathies.

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“… Acetazolamide Acetazolamide is a carbonic anhydrase inhibitor and its main use in skeletal muscle channelopathies is for the prophylactic treatment of periodic paralysis. It does, however, also have some antimyotonic properties demonstrated in a small open-label study of nine patients with NDM [ 40 ] as well as other case reports of chloride and sodium channel myotonias [ 4 , 41 , 42 ]. Indeed, one form of sodium channel myotonia has been labelled acetazolamide-responsive myotonia because of the effectiveness of the drug [ 43 ].…”

Section: Treatment Of Myotoniamentioning

confidence: 99%

Treatment Updates for Neuromuscular Channelopathies

Jitpimolmard

Matthews

Fialho

2020

Curr Treat Options Neurol

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Purpose of review This article aims to review the current and upcoming treatment options of primary muscle channelopathies including the non-dystrophic myotonias and periodic paralyses. Recent findings The efficacy of mexiletine in the treatment of myotonia is now supported by two randomised placebo-controlled trials, one of which utilised a novel aggregated n-of-1 design. This has resulted in licencing of the drug via orphan drug status. There is also good evidence that mexiletine is well tolerated and safe in this patient group without the need for intensive monitoring. A range of alternative antimyotonic treatment options include lamotrigine, carbamazepine and ranolazine exist with variable evidence base. In vitro studies have shown insight into reasons for treatment failure of some medications with certain genotypes opening the era of mutation-specific therapy such as use of flecainide. In the periodic paralyses, the ability of MRI to distinguish between reversible oedema and irreversible fatty replacement makes it an increasingly useful tool to guide and assess pharmacological treatment. Unfortunately, the striking efficacy of bumetanide in hypokalaemic periodic paralysis animal models was not replicated in a recent pilot study in humans. Summary The treatment of skeletal muscle channelopathies combines dietary and lifestyle advice together with pharmacological interventions. The rarity of these conditions remains a barrier for clinical studies but the example of the aggregated n-of-1 trial of mexiletine shows that innovative trial design can overcome these hurdles. Further research is required to test efficacy of drugs shown to have promising characteristics in preclinical experiments such as safinamide, riluzule and magnesium for myotonia or bumetanide for hypokalaemic periodic paralysis.

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Becker myotonia-a recently identified mutation in iberian descendants with apparent acetazolamide-responsive phenotype

Cited by 4 publications

References 8 publications

Ion Channel Gene Mutations Causing Skeletal Muscle Disorders: Pathomechanisms and Opportunities for Therapy

Ion Channel Gene Mutations Causing Skeletal Muscle Disorders: Pathomechanisms and Opportunities for Therapy

Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine

Treatment Updates for Neuromuscular Channelopathies

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