Carbon Monoxide in Tiny Doses Explored as an Ingestable Drug Therapy for Diabetic Retinopathy

Article: Small amounts of carbon monoxide may help protect vision in diabetes
Source: Augusta University, Medical College of Georgia
Published: November 4, 2021

Researchers are investigating the potential of small amounts of ingested carbon monoxide to reduce oxidative stress and inflammation, both precursors to retinal diseases like diabetic retinopathy. The compound, called HBI-002, is currently in early-stage clinical trials for sickle cell disease. Although we don't often consider carbon monoxide as occurring in our bodies, tiny amounts of carbon monoxide are actually produced endogenously by own cells and tissues as an antioxidant against oxidative stress and inflammation. For example, the enzyme heme oxygenase 1, a component of hemoglobin and immune cells, releases carbon monoxide (at an amount 1,000 times lower than what we inhale from the air) to reduce oxidative stress and inflammation as part of these cells' function, naturally upregulating the enzyme when there is tissue damage. Disease states such as diabetes disturb these natural mechanisms, thereby creating environments that are more prone to oxidative stress and inflammation. So "we have to think of ways to enhance, or reestablish, those mechanisms that would normally protect us," one of the principal investigators explains. The research team has been awarded a grant to further explore HBI-002’s potential. They plan to look at how the compound works in both an ischemic model of diabetic retinopathy and a model with more natural disease progression, with the hope of finding a noninvasive therapy for diabetic retinopathy.

Preliminary tests indicate that HBI-002 can "make the trip" in oral form all the way to the retina. The carbon monoxide is ingested as a liquid and becomes the more familiar gaseous state in the intestines, a unique liquid to gas transformation. There, it naturally binds to hemoglobin and travels along blood vessels to the retina. The researchers note that HBI-002 has no trouble finding hemoglobin; in fact, it is carbon monoxide's strong affinity for hemoglobin, blocking oxygen from binding, that causes its potentially fatal effects in high amounts. Once in the cells of the retina, the carbon monoxide finds heme oxygenase 1 and helps to induce the steps that yield its antioxidant, anti-inflammatory effects. If the benefits of HBI-002 continue to hold, the researchers then plan on further studying its mechanism of action, as well as optimal dosing and frequency for the compound. The retina a part of the body that has been thus far been difficult for oral (and topical) drugs to safely target, that is, without systemic and local adverse effects. The development of a safe, ingestable treatment for diabetic retinopathy could significantly relieve the burden of invasive therapies, as well as have implications for broader applications for vascular diseases in general.

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