Clinical Trial: Generation of a Cellular Model of CADASIL From Skin Fibroblasts

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Observational

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

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 Summary:
Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

Current Primary Outcome: Derivation of iPS cells from skin biopsies of patients with CADASIL [ Time Frame: 30 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Differentiation of iPS cells to vascular smooth muscle cells, phenotypic and mechanistic analyses [ Time Frame: 24 mois ]

Differentiation of iPS cells to vascular smooth muscle cells and phenotypic analysis (12 mois) Mechanistic analyses (12 mois)


Original Secondary Outcome: Same as current

Information By: Institut National de la Santé Et de la Recherche Médicale, France

Dates:
Date Received: January 3, 2014
Date Started: February 2014
Date Completion: August 2018
Last Updated: December 6, 2016
Last Verified: December 2016