التفاصيل البيبلوغرافية
| العنوان: |
Image_1_Therapeutic Potential of Sodium Channel Blockers as a Targeted Therapy Approach in KCNA1-Associated Episodic Ataxia and a Comprehensive Review of the Literature.JPEG |
| المؤلفون: |
Stephan Lauxmann (11412122), Lukas Sonnenberg (11412125), Nils A. Koch (11412128), Christian Bosselmann (11412131), Natalie Winter (5926814), Niklas Schwarz (8030486), Thomas V. Wuttke (8737782), Ulrike B. S. Hedrich (11412134), Yuanyuan Liu (136992), Holger Lerche (455372), Jan Benda (358720), Josua Kegele (11412137) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Neurology and Neuromuscular Diseases, Neurogenetics, episodic ataxia, sodium channel blockers, KV1.1, conduction-based model, voltage-gated potassium channels, riluzole, precision medicine, KCNA1 |
| الوصف: |
Introduction: Among genetic paroxysmal movement disorders, variants in ion channel coding genes constitute a major subgroup. Loss-of-function (LOF) variants in KCNA1, the gene coding for K V 1.1 channels, are associated with episodic ataxia type 1 (EA1), characterized by seconds to minutes-lasting attacks including gait incoordination, limb ataxia, truncal instability, dysarthria, nystagmus, tremor, and occasionally seizures, but also persistent neuromuscular symptoms like myokymia or neuromyotonia. Standard treatment has not yet been developed, and different treatment efforts need to be systematically evaluated. Objective and Methods: Personalized therapeutic regimens tailored to disease-causing pathophysiological mechanisms may offer the specificity required to overcome limitations in therapy. Toward this aim, we (i) reviewed all available clinical reports on treatment response and functional consequences of KCNA1 variants causing EA1, (ii) examined the potential effects on neuronal excitability of all variants using a single compartment conductance-based model and set out to assess the potential of two sodium channel blockers (SCBs: carbamazepine and riluzole) to restore the identified underlying pathophysiological effects of K V 1.1 channels, and (iii) provide a comprehensive review of the literature considering all types of episodic ataxia. Results: Reviewing the treatment efforts of EA1 patients revealed moderate response to acetazolamide and exhibited the strength of SCBs, especially carbamazepine, in the treatment of EA1 patients. Biophysical dysfunction of K V 1.1 channels is typically based on depolarizing shifts of steady-state activation, leading to an LOF of KCNA1 variant channels. Our model predicts a lowered rheobase and an increase of the firing rate on a neuronal level. The estimated concentration dependent effects of carbamazepine and riluzole could partially restore the altered gating properties of dysfunctional variant channels. Conclusion: These data strengthen the potential of SCBs to ... |
| نوع الوثيقة: |
still image |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/figure/Image_1_Therapeutic_Potential_of_Sodium_Channel_Blockers_as_a_Targeted_Therapy_Approach_in_KCNA1-Associated_Episodic_Ataxia_and_a_Comprehensive_Review_of_the_Literature_JPEG/16592411Test |
| DOI: |
10.3389/fneur.2021.703970.s002 |
| الإتاحة: |
https://doi.org/10.3389/fneur.2021.703970.s002Test |
| حقوق: |
CC BY 4.0 |
| رقم الانضمام: |
edsbas.5101253E |
| قاعدة البيانات: |
BASE |
