Unmet Need
Heart failure is a continuously growing health issue in the United States. According to a study by the CDC, approximately 6.2 million Americans had heart failure between the years 2013-2016, and that number is expected to breach 8 million by 2030 (see AHA). Acute decompensated heart failure (ADHF), a potentially fatal cause of respiratory distress, specifically occurs in ~1% of people over the age of 55 (see Chang). Treatment of ADHF differs from that of chronic heart failure, focusing on immediate hemodynamic stabilization rather than long-term symptom management (see UptoDate). Such stabilization often includes administration of vasodilators to reduce cardiac load, however use of vasodilators can also lead to hypotension in some patients (see UptoDate). Inotropes, drugs that increase cardiac contractility, can sometimes be given to prevent hypotension, but many have toxicities related to cAMP signaling (see Sabbah).
One promising way to overcome the complexities of ADHF treatment is to simultaneously vasodilate and increase cardiac contractility in a cAMP-independent manner, a goal accomplished by the nitroxyl donor Angelis’ salt (see Paolocci). However, Angelis’ salt degrades too rapidly under physiological conditions, thereby prohibiting its use as an ADHF therapeutic. Therefore, development of drugs that donate nitroxyl groups on a physiologically-relevant timescale could revolutionize the treatment of ADHF.
Technology Overview
Researchers at Johns Hopkins have developed a class of nitroxyl donor compounds based on diazen-1-ium-1, 2-diolate derivatives. These compounds degrade at one sixth the rate of Angelis’ salt, making the more relevant as potential treatments for ADHF.
