Carbon monoxide could treat pulmonary hypertension and inflammation

CARBON monoxide gets a bad rap. The gas, produced by incomplete combustion of hydrocarbons, causes hundreds of deaths every year by poisoning and sends many thousands to hospital. These are mainly the result of leaking cooking and heating equipment, but the colourless, odourless and tasteless substance, known to chemists as CO has also aided many a suicide. Most horrifically, Nazis used it in gas chambers.

But there is more to the “silent killer”, as CO is sometimes called. It is produced by many cells in the human body, where its molecules play a crucial role in activating enzymes involved in controlling the dilation of blood vessels, and thus blood flow. Mice in which the gene for producing the compound has been knocked out develop faulty organs and tend to die prematurely.

Exploiting this insight, researchers have successfully used CO to treat a number of ailments in lab critters. These include pulmonary hypertension, an otherwise incurable disease in which thickened arteries obstruct the flow of blood, leading to heart failure. The gas also keeps inflammation in check, in particular following organ transplants, where the recipient’s immune system tries to fend off the alien graft.


The reason human patients have so far been unable to benefit from any of this is CO’s gaseous nature. That makes it difficult to deliver in the right amounts to the parts of the body that need it. The problem is exacerbated by CO’s narrow “therapeutic index”; pump too little in and it won’t work, overshoot and it causes harm by binding irreversibly to haemoglobin, making less of this substance available to carry oxygen around the body.

Frederick Montgomery and Duncan Bathe think they have come up with a way to hit the sweet spot. Their Coke-can-sized gizmo, which they devised while working at Ikaria, an American drug firm that both have since left, contains a cartridge of pressurised CO, a tube to deliver the gas to the patient’s nose, and a few buttons to set the required dose. A sensor connected to a nozzle at the end of the tube constantly measures the patient’s breathing rate and adjusts the amount of CO dispensed with each breath. A slew of safety features, including automatic shutdown if anything seems amiss, are meant to eliminate the risk of CO overdose and ensure that none leaks out, endangering others.

Scientists at another American pharmaceutical company, Sangart, meanwhile, have been encasing the gas—or, strictly speaking, CO-ferrying haemoglobin—in a polymer pouch. Kim Vandegriff and her colleagues have been using polymer wrappers a mere nanometre (a billionth of a metre) across. These can be engineered to break open only where its CO load is needed. Early trials have shown promise in treating sickle-cell anaemia, a disease caused by a faulty haemoglobin gene.

Unlike most drugs, CO is not broken down by the body. Instead, once its job is done, it is trasported to the lungs and exhaled. As a result, it produces no side effects. Given the right dose, then, it can heal silently, too.

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Originally published :
http://www.economist.com/blogs/babbage/2012/07/drug-delivery-0?fsrc=scn/tw/te/bl/silenthealer