A molecule designed to mimic an enzyme can fight against highly reactive molecules that contribute to arthritis and other inflammatory conditions, according a report in Science today .
The body protects against corrosive superoxide radicals by deploying superoxide dismutase (SOD), a family of enzymes that Defang superoxide by converting it into molecular oxygen and hydrogen peroxide. In fact, SOD themselves once resembled promising candidates for treating inflammatory conditions such as rheumatoid arthritis. But they have been shown to trigger adverse immune reactions in some patients; Furthermore, like other proteins, native SOD is rapidly decomposed by enzymes of many proteins that destroy the body.
To get to another compound, a team led by Daniela Salvemini pharmacologist and chemist Dennis Riley Pharmaceuticals Metaphor in St. Louis started with manganese, less toxic of the three metals that can duplicate the catalytic activity SOD. Through trial and error, the researchers produced a ring structure that holds the manganese reasonably well. Then, by computer modeling and with many animal tests, they developed a derivative that was more stable and more efficient to break superoxide.
This compound, known as the M40403, converts superoxide at rates similar to those of native SOD and does not break down in the body. When injected into rats, M40403 sharply several key indicators of inflammation such as swelling, tissue damage, and the accumulation white blood cells to a wound site. In another series of tests on animals, M40403 reduces injury "reperfusion" which occurs when thrombolytic drugs are used to treat a heart attack or stroke.
M40403 is not the first non-protein SOD researchers have identified imitate, but it is more accurate to its action as the others. "They took a prototype drug and shown that it has a therapeutic activity in animals," said John Groves, a chemist at Princeton University . Salvemini said the team hopes to conduct safety studies and determine whether the compound has therapeutic value in people.
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