JUL 24, 2018 11:08 AM PDT

An Inhibitory Compound 'ITI-214' Shows Promising Effects for Heart Failure Patients

WRITTEN BY: Nouran Amin

According to early studies on animals at John Hopkins School of Medicine, a current drug examined in clinical trials to treat symptoms of Parkinson's disease may actually treat heart failure. The drug in question is called ITI-214 which is member of a class of compounds by the name of phosphodiesterase (PDE) type I inhibitors. ITI-214 has showed astounding effects on dog and rabbit hearts including isolated rabbit heart cells. Effects include an increase in the strength of heart muscle contractions. The recent study, published in the journal of Circulation, has shown that this particular drug holds a different mechanism of treatment than the current drugs used for treating heart failure concluding that the studied drug may actually be a safe way to increase heart contraction. For example, when researchers compared the effects of ITI-214 on isolated heart muscle cells to the effects of another class of PDE inhibitors known as PDE3, the two drugs worked differently. "Our results are intriguing because so far it's been largely uncharted territory to come up with a way of increasing contractility that doesn't ultimately hurt patients," explains David Kass, M.D., the principal investigator of the research study as well as a cardiology professor at Johns Hopkins University School of Medicine.

A chronic condition, heart failure is marked by the weakening of the heart muscle and its inability to effectively pump enough blood. Although plenty of drugs exist to treat, manage, and improve symptoms of heart failure, the drugs that increase the strength of the heart muscle contractions, for example dobutamine, may result in risky side effects such as an irregular heartbeat.

ITI-214 works to inhibit the function of an enzymatic protein; PDE1, part of the phosphodiesterase (PDE) family of over 100 proteins. All PDE proteins biochemically target one or both of two molecules: cAMP and cGMP. These molecules serve as intracellular molecular messengers. However, using ITI-124, which is a PDE inhibitor, it will work by stopping the breakdown of cAMP and cGMP. In heart failure, the presence of PDE activity limits the positive effects of cAMP or cGMP, so a PDE inhibitor, such as ITI-124, has the potential to be therapeutic. "We were pretty agnostic about what we would find and didn't necessarily expect anything that novel," says Kass. "To my knowledge, no study had reported increased heart contraction strength from a PDE1 inhibition before. But then, all of the prior studies where this might have been tested had used mice, and we knew that a different PDE1 form was found in larger mammals and humans. So, we just had to try it, and the results were very interesting. The new drug (ITI-24) produced many of the same heart and artery changes that PDE3 inhibitors do, so we naturally worried whether it worked in a similar way and might also have complications. So we tested them side by side."

ITI-214 is currently examined in clinical trials on heart failure patients at Johns Hopkins Medicine and Duke University. The drug has passed phase 1 safety trials in clinically healthy individuals.

 

Source: Johns Hopkins Medicine

About the Author
BS/MS
Nouran is a scientist, educator, and life-long learner with a passion for making science more communicable. When not busy in the lab isolating blood macrophages, she enjoys writing on various STEM topics.
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