Cellular Reprogramming as a Tool to Characterise the Cellular Electrophysiology of Familial Arrhythmia
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Eletrophysiology of iPS-derived Cardiomyocytes
- Sponsor
- University of Dundee
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Derivation of iPS cells
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Hereditary cardiac arrhythmias (genetically caused disturbances of heart rhythm) are life threatening conditions affecting otherwise healthy young individuals. Due to the inaccessibility of heart tissue, the abnormal electrical current(s) in the heart cells causing the rhythm disturbance can be difficult to study in detail and therefore in many cases remain untreatable. The investigators propose to study heart cell electrical function from such patients by reprogramming skin cells to become stem cells and then differentiating them to heart muscle cells.
The hypothesis of the study is that the differentiated cardiac cells will display electrical abnormalities dependent on the mutation causing the disease. These abnormalities can therefore provide a clue as to the nature of the mutation causing the disease or information about its effective management
Investigators
Eligibility Criteria
Inclusion Criteria
- •Clinical features of Brugada Syndrome (ECG findings)
- •mutation positive or mutation negative
- •Idiopathic ventricular fibrillation
Exclusion Criteria
- •not able to give informed consent
- •Age less than 18 years
- •clinical diagnosis ambiguous
Outcomes
Primary Outcomes
Derivation of iPS cells
Time Frame: 12 months
Induced pluripotent cells will be derived from all participants in the study. Differences in the efficiency of iPS cell generation from different patients will be recorded, and correlated with disease status and age. iPS cell generation will be confirmed by pluripotency markers (stable endogenous gene expression of Nanog, Oct4, Sox2; colony formation; expression of SSEA4) and ability to differentiate in the absence of self-renewal stimulus (ability to self-renew in the absence of self-renewal stimulus -loss of markers above)
Secondary Outcomes
- Electrophysiology on iPS-derived cardiomyocytes(12 months)
- Differentiation of iPS cells to cardiomyocytes(12 months)