Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome.

By |2020-09-08T18:24:56-05:00September 4th, 2020|Categories: DSF Research Review|Tags: , , , |

Just last month, a previous research review detailed how Stoke Therapeutics developed their targeted augmentation of nuclear gene output (TANGO), utilizing anti-sense oligonucleotides (ASOs) to upregulate expression of several genes, including SCN1A, in human cells and mouse brain. ASOs are single-stranded RNAs that bind to target RNA sequences and have the potential to alter the [...]

Focal epilepsy in SCN1A-mutation carrying patients: is there a role for epilepsy surgery?

By |2020-08-23T23:03:55-05:00August 28th, 2020|Categories: DSF Research Review|Tags: , , , |

In this brief report published in June, Vezyroglou et al detail the results of epilepsy surgery for focal seizures in 8 patients carrying mutations in the SCN1A gene that were predicted to be causal. Three of the 8 patients had a clinical diagnosis of Dravet syndrome. The surgical procedures were successful in reducing or eliminating [...]

Electrophysiological alterations of pyramidal cells and interneurons of the CA1 region of the hippocampus in a novel mouse model of Dravet syndrome

By |2020-08-24T12:16:38-05:00August 24th, 2020|Categories: DSF Research Review|Tags: , , , |

In this paper, Dyment et al detail a new mouse for the study of Dravet syndrome modeled after a patient mutation. This particular mutation (H939R) does not result in the typical haploinsufficiency where Nav1.1 sodium channel levels are reduced, but rather appears to affect the function of one copy of the sodium channel. Consistent with [...]

Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: Analysis of an ongoing long-term open-label safety extension study

By |2020-08-24T12:35:41-05:00August 24th, 2020|Categories: DSF Research Review|Tags: , , , |

FINTEPLA (fenfluramine) was recently approved by the FDA for the treatment of seizures in Dravet syndrome. The FDA required Zogenix, Inc to include a black box warning on the label because fenfluramine belongs to a class of drugs that affect a specific serotonin receptor (5-HT2B), and these types of drugs have previously been associated with valvular [...]

Aberrant regulation of a poison exon caused by a non-coding variant in Scn1a-associated epileptic encephalopathy

By |2020-08-17T11:28:47-05:00August 19th, 2020|Categories: DSF Research Review|Tags: , , , |

In late June 2020, Voskobiynyk et al shared their recent manuscript on bioRxiv (pre-print before peer-review) detailing a novel mouse model of Dravet syndrome that carries the same mutation in a non-coding region as a patient diagnosed with Dravet syndrome. “Non-coding” means that the mutation is not located in an area of the DNA that [...]

Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression

By |2020-09-04T01:54:18-05:00August 13th, 2020|Categories: DSF Research Review|Tags: , , , |

Stoke Therapeutics published a paper in Nature Communications detailing the mechanism of action for their new TANGO (targeted augmentation of nuclear gene output) therapy that utilizes ASO (antisense oligonucleotide) technology. While the applications of this technology have been discussed in presentations and meetings, this is the first publication detailing how it was developed. Cells use [...]

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