Unmet Need:
According to a survey by the CDC, nearly 50% of Americans age 20 and up have some form of cardiovascular disease (see AHA). The management of cardiovascular diseases depends on the specific indication, and standard therapies include one or multiple of the following types of medications: blood thinners, ACE inhibitors, beta-blockers, calcium channel-blockers, and cholesterol-lowering medications (see Everyday Health). Despite the availability of these various drugs, nearly 18 million people still die as a result of cardiovascular diseases each year, accounting for about 32% of deaths worldwide (see WHO). Development of innovative therapies with novel mechanisms of action could expand the number of available medications for management of cardiovascular diseases and help prevent some of these deaths.
One such novel mechanism is the recently discovered physiological roles of hydrogen sulfide (H2S). Naturally occurring H2S helps reduce oxidative stress in the body, and it plays roles in the relaxation of blood vessels, reduction of atherosclerotic plaque formation, and creation of new blood vessels, all of which are protective against cardiovascular diseases. Additionally, H2S helps protect the body from neurodegenerative disorders, gastrointestinal disorders, and cancer (see Wallace). Some molecules are being studied for their therapeutic potential as H2S donors, however their H2S release rates can be difficult to control, thereby limiting therapeutic relevance (see Zaorska). As an alternative to direct H2S release, future drugs could act through creation of hydropersulfides, the known mechanism of H2S action in the body (see Filipovic). As such, there is a strong need for development of drugs that can create hydropersulfides and therefore be used as therapeutics for cardiovascular and other diseases.
Technology Overview:
Researchers at Johns Hopkins have developed a class of molecules that act as hydropersulfide precursors. They have demonstrated that alteration of different side chains can finely tune the kinetics of hydropersulfide formation, causing faster or slower molecular action. This tunability could potentially be translated into therapeutic duration, thus enabling physiologically relevant treatment of disease.
Stage of Development:
The developed molecules have shown to increase hydropersulfide levels, as well as protect against oxidative stress in cardiac cells. Pre-clinical experiments are currently underway.
Publication:
Khodade et al. Chemical Science. 2021. 12, 8252-8259.
Pharoah, et al. Redox biology vol. 60 (2023): 102625.
