Generation of a Cellular Model of CADASIL From Skin Fibroblasts

Obtention d'un modèle Cellulaire de la Maladie CADASIL à Partir de Fibroblastes cutanés de Patients

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02032225

Enrollment

Registered

2014-01-09

Start date

2014-02-28

Completion date

2015-02-11

Last updated

2025-05-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

CADASIL

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.

Interventions

OTHERSkin biopsy

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

30 Years to 60 Years

Healthy volunteers

Inclusion criteria

: * Between 30 and 60 years; * Having a social security scheme or, CMU ; * Diagnosis of CADASIL confirmed by molecular analysis performed previously (missense mutation in the Notch3 gene affecting the number of cysteine in one of the 34 EGFR of NOTCH3 ) ; * No countra-indication for a skin biopsy (ongoing treatment with anti-coagulant, history of bleeding disorder or deficiency of blood clotting factors) ; * Written consent given.

Exclusion criteria

: * Patients without social security scheme or, CMU ; * Patients aged under 30 or over 60 years at the time of the first visit ; * Pregnant women beyond the 5th month of pregnancy * Patients who are not able to give informed consent ; * Countra-indication to the achievement of the skin biopsy ( ongoing treatment with anti- coagulant, history of bleeding disorder or deficiency of coagulation factors ) .

Design outcomes

Primary

Measure	Time frame
Derivation of iPS cells from skin biopsies of patients with CADASIL	30 months

Secondary

Measure	Time frame	Description
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)

Countries

France

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026