Study suggests a drug treatment for abdominal aortic...( drugcontained two and one-half times a...),Health

drug contained two and one-half times as much MMP-9 protein as those from the doxycycline-treated patients. And they contained five and one-half times as much messenger RNA for MMP-9. This messenger carries the blueprint for MMP-9 from the gene to the cellular machinery that makes the enzyme. "So doxycycline decreases MMP-9 production," Curci says.

He also showed that the drug decreased the ability of cultured white cells to produce MMP-9 messenger RNA and MMP-9 protein.

Doxycycline had a different effect on MMP-2. Instead of decreasing its production, it inhibited its activation -- protein-degrading enzymes come with a safety cap that is removed only after they leave the cell. Curci determined that the aneurysm samples from the patients who had not taken doxycycline contained nearly one and one-half times as much of the active form of MMP-2 as the samples from the doxycycline-treated patients. "So in the body, doxycycline affects MMPs by a complex mixture of mechanisms," Curci says.

The drug's effect on the two MMPs resembles a military campaign involving ground troops as well as air attacks. "So doxycycline may have a distinct advantage over drugs that act simply as MMP inhibitors. The idea of using a drug that employs several mechanisms in concert is very attractive," Thompson says.

A pilot study at the School of Medicine and four other Midwest institutions now is testing the effects of a six-month course of doxycycline on the growth of AAAs. With those data, the researchers hope to persuade the National Institutes of Health to fund a clinical trial involving several hundred patients. "The remaining question is whether doxycycline therapy can reduce aneurysm growth in patients over a period of years," Thompson says. "If that proves to be the case, I would like to see everyone over 65 get an abdominal ultrasound so that those with abdominal aortic aneurysms can receive drug therapy instead of needing surgery or dying unexpectedly from a ruptured
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Contact: Linda Sage
sage@medicine.wustl.edu
314-286-0119
Washington University School of Medicine
7-Jun-1999

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