Familial Aortopathies and Cellular Exploration (FACE)

ACTA2 and Familial Aortopathies: Creation and Validation of an Exploratory Cellular Model

The prevalence of hereditary aortic disease (HTAD), responsible for aneurysm or dissection, is estimated at 25%. Mutations in the ACTA2 gene represent the main cause of non-syndromic forms (10-21%). ACTA2 is expressed in vascular wall smooth muscle cells (VSMC) and encodes alpha actin (α-SMA). This actin isoform is in the majority in VSMCs and plays a key role in their contractile properties. The mutations are dominant-negative and lead, in a fibroblast model, to defects in the organisation of the actin cytoskeleton and to an increase in the migratory and proliferative potential of the cells. In vivo, VSCMs exist in a phenotypic continuum ranging from a quiescent differentiated contractile state to a so-called synthetic state in which cells are proliferative, synthesise extracellular matrix elements and exhibit enhanced migratory capabilities. To understand how ACTA2 mutations deregulate VSMC functions and steer them towards a synthetic phenotype, it is necessary to have a cellular model as close as possible to the affected tissue..

Study Overview

• Status: Not yet recruiting
• Conditions: Familial Aortopathies
• Intervention / Treatment: Biological: blood sample

• Study Type: Interventional
• Enrollment (Anticipated): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laurence Bal, MD; Email: laurence.bal@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13005
    • Assistance Publique Hopitaux de Marseille
    • Contact: Laurence Bal, MD; Email: laurence.bal@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patient with a mutation in the ACTA2 gene

Exclusion Criteria:

• patient under 18 years of age at the time of inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: familial aortopathy	Biological: blood sample; blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
analysis of the impact of ACTA2 mutations on the morphology of the actin cytoskeleton	use of a model of IPS cells reprogrammed into VSMCs from patients with ACTA2 mutations, compared to a healthy control	baseline

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: François CREMIEUX, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Actual): June 2, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: RCAPHM22_0100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No