Sexually Divergent Mortality and Partial Phenotypic Rescue after Gene Therapy in a Mouse Model of Dravet Syndrome

By |2020-01-08T14:03:37-05:00January 8th, 2020|Categories: DSF Research Review|Tags: , , |

Dravet syndrome is caused by a mutation in the SCN1A gene, which codes for the NaV1.1 sodium channel a subunit. As described in previous summaries, gene therapy is becoming a very promising approach for fixing genetic disorders, with the use of adeno-associated virus ("AAV") as the preferred delivery system - but the coding region [...]

Profound Reduction in Seizure Frequency (≥75%) Leads to Improved Everyday Executive Function: Analysis From a Phase 3 Study of ZX008 (Fenfluramine HCl) in Children/Young Adults With Dravet Syndrome

By |2020-01-08T14:08:26-05:00January 8th, 2020|Categories: DSF Research Review|Tags: , , |

This month my literature survey returned a poster that was presented at the recent American Epilepsy Society meeting. Although this is not a peer-reviewed journal article, I include it because it is interesting, and I have no concerns about its legitimacy. In previous summaries, the story of fenfluramine has been presented; along with some [...]

SCN1A variants in vaccine-related febrile seizures: a prospective study

By |2019-12-17T12:41:21-05:00December 17th, 2019|Categories: DSF Research Review|Tags: , , |

Prolonged febrile seizures (that is, seizures triggered by a fever) are a manifestation of Dravet syndrome. Vaccination is a highly effective public health approach that has led to reduced childhood morbidity and mortality from many infectious diseases, and has an excellent safety profile, but in rare cases can be followed by febrile seizures. Given [...]

SCN1A variants from bench to bedside – improved clinical prediction from functional characterization

By |2019-12-17T12:46:54-05:00December 17th, 2019|Categories: DSF Research Review|Tags: , , |

Dravet syndrome is caused by mutations in the SCN1A gene, which encodes for the voltage-gated sodium channel Nav1.1 - a protein that participates in conduction of nerve signals. Thousands of different SCN1A mutations have been reported, but only a small number of these have been characterized functionally. This is unfortunate, because some SCN1A mutations [...]

Stiripentol: A Review in Dravet Syndrome

By |2019-11-12T12:55:08-05:00November 12th, 2019|Categories: DSF Research Review|Tags: , , |

This article is a summary of the efficacy and safety of stiripentol (Diacomit), a drug indicated for use in patients with Dravet syndrome as an adjunctive therapy in conjunction with clobazam (Onfi) and valproate (Depakote). Stiripentol was first reported to be helpful in Dravet syndrome in 2000, and was approved in the EU in [...]

Early hippocampal hyperexcitability followed by disinhibition in a mouse model of Dravet syndrome

By |2019-11-12T13:54:07-05:00November 12th, 2019|Categories: DSF Research Review|Tags: , , |

Dravet syndrome can be conceptualized as a three-stage disease - the first stage (febrile; up to age 1) is typically characterized by prolonged complex febrile seizures and status epilepticus; followed by a second stage (worsening; up to age 5) which is characterized by the appearance of additional seizure types (e.g. generalized motor, atypical, myoclonic, [...]

Fenfluramine HCl (Fintepla®) Provides Long-Term Clinically Meaningful Reduction in Seizure Frequency: Results of an Open-Label Extension Study

By |2019-10-10T09:44:24-05:00October 10th, 2019|Categories: DSF Research Review|Tags: , , |

This is a report on results from an open-label extension study of fenfluramine in children and young adults (2–18 years old) with Dravet syndrome. "Open-label extension" means that the participants have participated in the Phase 3 clinical trial and are continuing with the drug, but can know information that was previously blinded, such as [...]

dCas9-based Scn1a gene activation restores inhibitory interneuron excitability and attenuates seizures in Dravet syndrome mice

By |2019-10-10T09:51:34-05:00October 10th, 2019|Categories: DSF Research Review|Tags: , , |

Our chromosomes are paired, and therefore we have two copies of almost every gene. The mutations that cause Dravet Syndrome affect only one copy of the Scn1a gene, which leads to production of only half the normal amount of Nav1.1 protein. New gene therapy approaches are starting to have success replacing mutated gene copies [...]

Reduced efficacy and risk of seizure aggravation when cannabidiol is used without clobazam

By |2019-10-10T10:10:57-05:00October 10th, 2019|Categories: DSF Research Review|Tags: , , |

Cannabidiol oral solution (Epidiolex) was recently approved in the United States for the treatment of seizures associated with Dravet syndrome. It is typically used as an adjunct with other medication(s). This paper highlights the observation that the effect of cannabidiol is significantly increased when used in conjunction with clobazam (a.k.a. "Onfi"), and it raises [...]

Gait abnormalities in people with Dravet syndrome: A cross-sectional multi-center study

By |2019-10-10T11:53:21-05:00October 10th, 2019|Categories: DSF Research Review|Tags: , , |

In reviews of Dravet syndrome, statements about gait are usually very generalized, along the lines of: " by the age of 13 years, up to 80% of people with Dravet syndrome walk with a crouch gait". However, it would be useful to have a more specific, and detailed, description, which is what the current [...]