Approved Research

ORAI1 in cardiovascular and metabolic disease

Lay summary

We use cells from patients and animal models of key human cardiovascular diseases such as heart failure, aneurysm, atherosclerosis and pulmonary hypertension. During these experiments we have found evidence of a new and exciting target: ORAI1. It is a calcium channel expressed in a wide range of cell types that are important in these human diseases. Inhibition at this target seems to be beneficial. We have developed a small molecule inhibitor of ORAI1 (a starting point for developing a human drug to treat these diseases). However, evidence implicating ORAI1 in human cardiovascular disease is lacking and clear evidence is required before we embark on a high cost drug development programme.

This project therefore seeks to use UK Biobank to look for associations between ORAI1 mutations and human cardiovascular disease in the areas we have studied in the preclinical setting. Over 12 months we will search UK Biobank for ORAI1 mutations linked to heart failure, aortic aneurysm/dissection, pulmonary hypertension and atherosclerosis. Once we find mutations, we will create these mutations in cells in the lab and test the function of them. This will then place us in a strong position to seek major funding to develop our inhibitors into drugs for human trials. Our hope is that this will lead to a new medical treatment for at least one of these important cardiovascular diseases.