Generation of a Cellular Model of CADASIL From Skin Fibroblasts

Institut National de la Santé Et de la Recherche Médicale, France

Status: Completed

Conditions: CADASIL

Treatments: Other: Skin biopsy

Study type: Observational

Funder types: Other

Identifiers

NCT02032225

C13-34

2013-A00994-41 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 30 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 ) .

Trial design

8 participants in 1 patient group

CADASIL

Description:

patients with CADASIL

Treatment:

Other: Skin biopsy