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NCT06371794: EXEDRA

EXploring novEl Molecular Determinants of DRAvet Syndrome Phenotype Heterogeneity

ENROLLING BY INVITATION NA Last updated 17 April 2024
What this trial tests

NA trial testing skin punch biopsy in Dravet Syndrome in 16 participants. Enrolling by invitation.

Timeline
6 July 2023
Primary endpoint
30 April 2025
31 May 2026

Quick facts

Lead sponsorFondazione Policlinico Universitario Agostino Gemelli IRCCS
PhaseNA
StatusENROLLING BY INVITATION
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposebasic science
Enrollment16
Start date6 July 2023
Primary completion30 April 2025
Estimated completion31 May 2026
Sites1 location across Italy

Drugs / interventions tested

Conditions studied

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Who can join

Adults 18 to 35, any sex, with Dravet Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Dravet syndrome is characterized as a developmental encephalopathy resulting from mutations of SCN1A, the gene encoding the alpha subunit of the voltage-gated sodium channel Nav1.1. The syndrome typically presents with drug-resistant epilepsy and varying degrees of cognitive disorders. Current treatment efficacy may be hindered by insufficient knowledge of undiscovered molecular determinants of the disease and its heterogeneous nature. Utilizing induced pluripotent stem cells (iPSCs) derived from skin biopsies, accessibility to patients' brain neurons has enabled successful modeling of various genetic neurological diseases. Neurons and brain organoids will be obtained from Dravet syndrome patients exhibiting diverse phenotypic severities, encompassing behavioral and developmental delays, to discern the molecular determinants of phenotypic diversity. Specifically, emphasis will be placed on investigating cellular and molecular mechanisms linking altered neuronal excitability with synaptic dysfunction.The study will focus on exploring the expression of newly identified modifiers potentially associated with neuronal excitability and synaptic function in iPSC-derived human neurons. This aims to establish correlations between the severity of epileptic and cognitive phenotypes and the altered expression of these proteins, whose functions are not fully understood.In the mid to long term, efforts will be directed towards overcoming the limitations of conventional therapeutic approaches for Dravet syndrome. This will involve attempting to reverse the observed morphological and functional alterations in Dravet syndrome neurons using viral vectors to promote overexpression/downregulation of identified modifiers correlated with disease severity. The anticipated outcomes of this project are expected to unveil novel molecular mechanisms underlying the pathophysiology of this severe neurogenetic disease, characterized by varying degrees of cognitive impairment. Moreover, these findings may pave the way for the discovery of innovative therapeutic strategies.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.

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Other recruiting trials for Dravet Syndrome

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Data sources for this page

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