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Record W4382048782 · doi:10.1080/14728222.2023.2230364

SCN1A as a therapeutic target for Dravet syndrome

2023· review· en· W4382048782 on OpenAlexaff
Kenneth A. Myers

Bibliographic record

VenueExpert Opinion on Therapeutic Targets · 2023
Typereview
Languageen
FieldMedicine
TopicEpilepsy research and treatment
Canadian institutionsMcGill University Health CentreMontreal Children's Hospital
Fundersnot available
KeywordsDravet syndromeMedicineEpilepsyPediatricsEncephalopathyEpilepsy syndromesSodium channel blockerDiseaseBioinformaticsSodium channelPsychiatryInternal medicineBiology

Abstract

fetched live from OpenAlex

Introduction Dravet syndrome is a severe early infancy-onset developmental and epileptic encephalopathy. Patients have drug-resistant seizures, as well as significant co-morbidities, including developmental impairment, crouch gait, sleep disturbance, and early mortality. The underlying cause is mutations in SCN1A, encoding the sodium channel subunit NaV1.1, in >90% of patients. At present, approved Dravet syndrome treatments are symptomatic, primarily aimed at reducing seizure frequency, but having little to no effect on co-morbidities.Areas covered We discuss the potential to treat Dravet syndrome by targeting NaV1.1 directly. Anti-seizure medications that act as sodium channel inhibitors are generally minimally effective and can actually exacerbate seizures. However, other interventions are currently under investigation, including gene therapies that increase the amount of functional NaV1.1. Some of these interventions have encouraging pre-clinical data from in vitro and animal models.Expert opinion Increasing functional NaV1.1 via antisense oligonucleotides or virus-borne vectors is the most promising avenue for meaningful improvement in Dravet syndrome treatment, with the potential to not only reduce seizures but also address the multiple co-morbidities associated with this disease. However, human clinical trial data are necessary to determine safety and to clarify if, and to what extent, these interventions modify the natural history of Dravet syndrome.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.979
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0010.004

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.158
GPT teacher head0.452
Teacher spread0.294 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; both teacher heads agree on what is shown here.

Study designNot applicable
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations10
Published2023
Admission routes1
Has abstractyes

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