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Generation of a Cellular Model of CADASIL From Skin Fibroblasts

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Disease Information

Descriptive Information
Brief Title † Generation of a Cellular Model of CADASIL From Skin Fibroblasts
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 Description
Study Phase N/A
Study Type † Observational
Study Design † Observational Model: Case-Only, Time Perspective: Prospective
Primary Outcome Measure † Derivation of iPS cells from skin biopsies of patients with CADASIL
Secondary Outcome Measure † Differentiation of iPS cells to vascular smooth muscle cells, phenotypic and mechanistic analyses
Condition † CADASIL
Intervention † OtherSkin biopsy
Study Arms / Comparison Groups CADASIL patients with CADASIL
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Other
Estimated Enrollment † 10
Start Date † February 2014
Completion Date August 2018
Primary Completion Date August 2018
Eligibility 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 ) .
Gender Both
Ages 30 Years - 60 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries † France
Administrative Information
NCT ID † NCT02032225
Organization ID C13-34
Secondary IDs †† 2013-A00994-41
Responsible Party Sponsor
Study Sponsor † Institut National de la Santé Et de la Recherche Médicale, France
Collaborators ††
Investigators † Principal Investigator: Anne JOUTEL, MD, PhD, Institut National de la Santé Et de la Recherche Médicale, France
Information Provided By
Verification Date December 2016
First Received Date † January 3, 2014
Last Updated Date December 6, 2016
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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