One-two punch helps explain greatest unmet need in cardiology
Nearly half of patients admitted to the hospital for heart failure have no treatment options. Cardiology researchers at UT Southwestern Medical Center have gained new insight into the underlying basis of the condition that points to a new approach that could help patients worldwide. Read story
Heart failure is one of only two forms of cardiovascular disease that's going up. In fact, the prevalence of heart failure is exploding around the world. They are two types of heart failure. If you have a heart attack and the front wall of your heart dies, the heart can't pump very well and the ejection fraction is reduced, HFrEF. That's about half the picture and we have probably 10 different things we can do for those patients. The other half of heart failure, the one that is increasing is where the heart is able to pump just fine. It's just so stiff that it can't fill. That's called heart failure with preserved ejection fraction and it is a disorder that effects hundreds of millions of people for which we have no therapies, nothing, zero. It's said to be the single, greatest unmet need in cardiology. We don't understand the underlying cause so we can go at the route of the problem. That's where our study, I believe, is a significant advance. Eighty percent of the people with HFpEF have high blood pressure. Something like sixty, seventy percent have diabetes. So they have a high blood pressure stress and a metabolic stress that converge so Gabrielli made mice that look like these people.
You look inside the cells to see what was going on in there. What we found was a molecular mechanism that was quite different from what we saw in other types of heart failure. And we were lucky enough to have access to human samples where we were able to go and look inside those cells as well. And we saw the same thing.
These insights that we have uncovered here actually explain why some of those clinical trails, of which there have been many, have failed because the objective was to deliver a compound that would raise nitric oxide, so called NO donors. What we found is that there is way too much NO because there's another pathway that people hadn't noticed that was making NO at a very high level. If you look at them carefully not only did they not work, they actually made the patient worse. And now we understand why. We know exactly where that NO is coming from, and a surgical strike on that enzyme with a drug or with a genetic manipulation makes that HFpEF better and there are FDA approved drugs that inhibit that enzyme. So we could envision translating this rapidly.