Small amounts of carbon monoxide might alleviate symptoms of multiple sclerosis, a study in mice suggests. The finding may offer a treatment for MS, which strikes when a person's immune system damages the fatty sheaths that protect nerve fibers in the brain and spinal cord.
At first glance, the approach seems fraught with problems. Carbon monoxide inhalation can be lethal. But the body makes the molecule naturally in small amounts when an enzyme called heme-oxygenase-1 (HO-1) breaks down a portion of the blood protein hemoglobin.
That enzyme might act as a brake to prevent inflammation from getting out of hand, says immunologist Miguel P. Soares of the Gulbenkian Institute of Science in Oeiras, Portugal. Previous studies showed that HO-1 is activated in the presence of inflammatory immune system cells and that carbon monoxide slows inflammation.
In patients with MS, inflammatory cells strip away myelin sheaths, and the subsequent nerve damage results in fatigue, poor balance, and loss of muscle control.
To find out whether the anti-inflammatory effect generated by HO-1 could limit myelin damage in the brain and spinal cord, Soares and his team tested mice that had a disease similar to MS. Animals receiving a drug that revs up HO-1 production showed far less myelin damage than did the other mice. Among mice paralyzed by the disease, most of those receiving the drug recovered movement. Mice given inert treatments failed to improve.
Furthermore, a group of mice with boosted HO-1 activity and another group that directly inhaled carbon monoxide had substantially fewer inflammation-causing immune T cells in their brains than did mice getting a placebo. The researchers report their findings in the February Journal of Clinical Investigation.
The study also showed that boosting HO-1 activity reduces the accumulation of inflammatory T cells on myelin sheaths. Further tests indicated that HO-1 and carbon monoxide keep other immune cells from activating the myelin-targeting T cells.
MS patients often have periods of remission, followed by a recurrence of symptoms. "These relapses probably occur because of a lack of sustained HO-1 [production]," Soares says.
However, neuropathologist Cedric S. Raine of the Albert Einstein College of Medicine in New York City says that the new study, while extensive, falls short of establishing a clear link between carbon monoxide and a dampened immune response. For example, he says, carbon monoxide toxicity might simply cause stress and induce the release of steroids, which suppress inflammation.
Meanwhile, research on carbon monoxide treatment "has become a very hot area," Soares says. Other studies of laboratory animals suggest that carbon monoxide eases inflammation in intestines, lungs, and blood vessels (SN: 2/22/03, p. 126: Available to subscribers at Carbon monoxide may limit vascular damage). Last year, U.S. scientists began recruiting participants for a study to gauge the effects of small doses of inhaled carbon monoxide on lung inflammation. But the best delivery method might be carbon monoxide–releasing drugs, which could be targeted to specific tissues, Soares says.
Cedric S. Raine
Albert Einstein College of Medicine
1300 Morris Park Avenue
New York, NY 10461
Miguel P. Soares
Instituto Gulbenkian de Ciência
Rua da Quinta Grande, 6
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For additional information about this clinical trial, go to [Go to].