Can a new drug improve blood flow to the limbs in peripheral arterial disease?

11ß-hydroxysteroid dehydrogenase type 1 inhibition as a novel treatment for peripheral arterial disease

Dr Patrick Hadoke is investigating whether a new drug he has developed boosts new blood vessel growth and improves blood flow to the limbs in people with peripheral arterial disease. People with peripheral arterial disease have a reduced blood supply to the feet and hands, resulting in pain, ulceration and gangrene. The condition is a major cause of disability and even death. There are very few effective treatments - surgery can help but is difficult in elderly patients and works less well in those with diabetes, in whom the disease is more common. We urgently need new treatments. Dr Hadoke and colleagues have developed a new drug, which blocks an enzyme called 11ß-HSD1. The team has developed the drug for use in diabetes, and in clinical trials have found that it reduces blood glucose, body weight and cholesterol (all risk factors for heart disease). In mice they have shown that the drug also boosts blood vessel growth in the heart after heart attack, improving heart function. Mice without the 11ß-HSD1 protein have much more blood vessel growth after ischaemia to the hind legs, when blood flow is restricted – a model of peripheral arterial disease. In this project, Dr Hadoke will establish in mice the molecular pathways underlying this enhanced blood vessel growth and whether these pathways are the same in human samples. He will study if blocking 11ß-HSD1 after blood flow is restricted in mice works as well as blocking the enzyme before blood flow restriction. This will allow Dr Hadoke to establish the time points at which the drug may be potentially useful in patients. If successful, the researchers hope to test the drug in atrial in patients, which, if successful, could make a huge difference to people living with peripheral arterial disease.