Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine.
Channelopathies
/ drug therapy
Humans
Hypokalemic Periodic Paralysis
/ drug therapy
Lamotrigine
/ therapeutic use
Mexiletine
/ therapeutic use
Muscle, Skeletal
/ drug effects
Mutation
Myasthenic Syndromes, Congenital
/ drug therapy
Myotonic Disorders
/ drug therapy
Precision Medicine
/ methods
Randomized Controlled Trials as Topic
Sodium Channel Blockers
/ therapeutic use
Non-dystrophic myotonia
calcium channel
chloride channel
congenital myasthenic syndrome
congenital myopathy
periodic paralysis
precision medicine
sodium channel
targeted therapy
Journal
Journal of neuromuscular diseases
ISSN: 2214-3602
Titre abrégé: J Neuromuscul Dis
Pays: Netherlands
ID NLM: 101649948
Informations de publication
Date de publication:
2021
2021
Historique:
pubmed:
17
12
2020
medline:
16
11
2021
entrez:
16
12
2020
Statut:
ppublish
Résumé
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. 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. 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. 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 CAI compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies. 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.
Sections du résumé
BACKGROUND
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
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
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
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 CAI compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies.
CONCLUSIONS
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.
Identifiants
pubmed: 33325393
pii: JND200582
doi: 10.3233/JND-200582
pmc: PMC8203248
doi:
Substances chimiques
Sodium Channel Blockers
0
Mexiletine
1U511HHV4Z
Lamotrigine
U3H27498KS
Types de publication
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
357-381Références
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