Could UDCA be a new antifibrotic therapy for chronic heart failure?
Translational Research Project Grant – Prof Julia Gorelik, Imperial College London
A heart attack is usually caused by the blockage of a coronary artery which cuts off the supply of blood to the heart muscle. This starves the heart muscle of oxygen and the heart may be permanently damaged. After the onset of damage, repair starts and special cells appear which form scar tissue. However, extensive scarring, or fibrosis, impairs coupling between muscle cells in nearby areas and the heart may start to beat irregularly.
The aim of this project is to test whether a drug that has shown beneficial effects in other organs can reduce the scarring of the heart. The drug, called UDCA, is a component of bile and is already used to treat other conditions and so is known to be safe. UDCA prevents the appearance of cells that play a part in the formation of scar tissue and also improves survival of muscle cells that have been subjected to a lack of oxygen. The team will use human donated hearts; some of them healthy and some failing and discarded after the patient has received a transplanted heart. They will culture isolated heart cells and slices of heart tissue in the lab, treat them with UDCA and compare signs of fibrosis in tissue from healthy and failing hearts.
Also, a small trial will be carried out involving patients with chronic heart failure, who are suffering from extensive fibrosis in their hearts. The patients will be divided into one group who will receive UDCA for three months and the other who will receive a placebo. At the end of the three month period, they will compare the distribution and amount of fibrosis in the heart muscle by cardiac MRI scans in the two groups of patients. The findings will show whether UDCA has potential as a protective treatment in heart failure patients.