Veterans Affairs

Carbon monoxide therapy for cardiovascular and inflammatory diseases

Compound generates carbon monoxide in the body using organic molecules

Medical & Biotechnology

The Department of Veterans Affairs has discovered a novel therapy with potential for cardiovascular and inflammatory diseases. The VA is seeking a health care company to develop it into an available treatment.

Carbon monoxide (CO) is well-known as a lethal, toxic gas. However, CO is also an important member of the gasotransmitter family of signaling molecules in mammals and has beneficial therapeutic effects.

Production of CO in a mammalian system occurs through the activity of heme oxygenases (HO-1 and HO-2). These enzymes regulate the catabolism of heme (the iron-containing compound which forms the nonprotein part of hemoglobin) and play an important role in the modulation of a variety of responses, such as stress response and circadian rhythm.

Studies have shown that CO has anti-inflammatory, antiproliferative, and anti-apoptotic effects. CO has been found to play a key beneficial role in various inflammatory-related disorders including inflammatory bowel disease (IBD), psoriasis, mid-ear infection-induced inflammation, uveitis, and burn- and injury-related inflammation. It has also been shown to positively affect cardiovascular disease.

A key issue in the use of CO as a therapeutic agent has been the safe delivery of low doses to the desired site of action. Toxicity, as well as the need to activate therapeutic molecules with ultraviolet light, has been a barrier to adoption with proposed approaches.

But VA researchers have developed a method to generate carbon monoxide-releasing molecules (CORMs) in the body with little or no toxicity and without the need for external stimuli.

In this approach, CO is produced from the reaction between the dienone tetraphenylcyclopentadienone (TPCPD) and the strained alkyne bicyclononyne. The molecules can be synthesized prior to administration (ex vivo) or formed after administration to a patient (in vivo). The reaction results in a stable, metal free, water-soluble, release of CO under physiological conditions.

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