Generation of a Cellular Model of CADASIL From Skin Fibroblasts

Completed

• Conditions: CADASIL
• Interventions: Other: Skin biopsy

• Registration Number: NCT02032225
• Lead Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Brief Summary

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy (CADASIL) is an archetypal small vessel disease of the brain caused by dominant mutations in the NOTCH3 receptor. Cardinal vascular lesions include deposition of granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells, progressive smooth muscle cell loss, and fibrosis of the media. Pathogenic mutations alter the number of cysteine residues in the extracellular domain of NOTCH3 (Notch3 ECD), leading to its abnormal accumulation in the GOM deposits. Vascular smooth muscle cell has been identified as the primary target cell in this disease. Pathophysiological processes leading from NOTCH3 mutations to smooth muscle cell loss remain poorly understood.

The investigators propose to study these mechanisms by reprogramming skin cells to become stem cells and then differentiating them to vascular smooth muscle cells.

The hypothesis of this study is that the differentiated smooth muscle cells will display the characteristic features of CADASIL, ie, Notch3 ECD accumulation and GOM deposits.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-01-03
• Study First Submitted QC: 2014-01-07
• Study First Posted: 2014-01-09
• Study Start: 2014-02
• Primary Completion: 2015-02-11
• Study Completion: 2015-02-11
• Status Verified: 2016-12
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CADASIL	Skin biopsy	patients with CADASIL

Primary Outcome Measures

Name	Time	Method
Derivation of iPS cells from skin biopsies of patients with CADASIL	30 months

Secondary Outcome Measures

Name	Time	Method
Differentiation of iPS cells to vascular smooth muscle cells, phenotypic and mechanistic analyses	24 mois	Differentiation of iPS cells to vascular smooth muscle cells and phenotypic analysis (12 mois) Mechanistic analyses (12 mois)

Trial Locations

Locations (1)

INSERM; 🇫🇷 Paris, France