Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 24, Issue 20, Pages 2264-2282Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612824666180723161811
Keywords
Heme oxygenase; therapeutic gas; gasotransmitter; carbon monoxide; CORM; anesthetics
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Funding
- NIH [R44 DK111260-01]
- Department of Defense [W81XWH-16-0464]
- Alexander von Humboldt foundation
- Bavarian Ministry of Economic Affairs and Media, Energy and Technology (Validierungsforderung)
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R44DK111260] Funding Source: NIH RePORTER
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Heme oxygenase (HO), the rate-limiting step in the degradation of heme to biliverdin, ferrous ion, and carbon monoxide (CO), is an ancestral protective enzyme conserved across phylogenetic domains. While HO was first described in the late 1960s and progressively characterized in the following decades, there has been a surge of innovation over the past twenty years in efforts to leverage the cytoprotective power of HO in a clinical setting. Despite the plethora of preclinical data indicating extraordinary therapeutic potential, HO has remained elusive from the physician's toolbox. The leading candidate in development, CO, has long been misconstrued as a useless toxic gas. Scientists have crafted an array of CO delivery molecules and devices to harness HO, however, each endeavor was met with limitations preventing translation into clinical practice. In this discussion, we summarize the HO / CO field with a clinical and commercial development perspective. More specifically, given the enormous global efforts and capital investment into the field, we ask: where is the breakthrough therapy?
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