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| ID | Type | Description | Link |
|---|---|---|---|
| T13/21 | Other Grant/Funding Number | Tenovus Tayside |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hereditary VF | Patients with hereditary ventricular fibrillation, negative for known mutations | ||
| Brugada | Patients suffering from Brugada syndrome |
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| Measure | Description | Time Frame |
|---|---|---|
| Derivation of iPS cells | 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) | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Differentiation of iPS cells to cardiomyocytes | The ability of each iPS cell line to differentiate into spontaneously beating cardiomyocytes will be assessed. Efficiency of differentiation per lina and per patient will be recorded. | 12 months |
| Electrophysiology on iPS-derived cardiomyocytes |
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Inclusion Criteria:
Exclusion Criteria:
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Arrhythmic patients participating in the Familial Arrhythmia Network Scotland (FANS)
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| Name | Affiliation | Role |
|---|---|---|
| Marios P Stavridis, PhD | University of Dundee | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Dundee | Dundee | Angus | DD1 9SY | United Kingdom |
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| ID | Term |
|---|---|
| D014693 | Ventricular Fibrillation |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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Skin biopsies will be extracted and used to derive fibroblasts. These will be retained and reprogrammed to iPS cells (also to be retained). Derived cell lines are not considered a tissue under the UK Human Tissue Act
Ability to collect electrophysiological measurements from iPS-derived cardiomyocytes will be asssessed. Resting membrane potential, Ca2+, K+ current function and sponteneous and induced depolarisation will be measured per line and per patient. Correlations with patient disease phenotype will be recorded. |
| 12 months |
| D013568 |
| Pathological Conditions, Signs and Symptoms |