Statin drugs taken by millions of people to control high cholesterol may also be used to treat a blood vessel disorder that can lead to sometimes fatal strokes, seizures, paralysis and other problems, University of Utah School of Medicine researchers have discovered.
Cerebral cavernous malformation (CCM) is a surprisingly common and potentially dangerous condition that leads to abnormal blood vessels in the brain, said Kevin Whitehead, a cardiologist and assistant professor of internal medicine. Currently, the only option for treating CCM, which strikes every one in 200 people, is to perform neurosurgery.
"There is no medicine that was known that can change the way these things behave," he said.
Using U. Nobel laureate Mario Capecchi's knock-out gene technology in mice, Whitehead and his colleagues were able to breed mice lacking the Ccm2 gene, one of three genes associated with the disease.
Without the gene, the mice developed a problem with their endothelium -- a thin, inner lining of cells that forms a blood vessel's tubular passage for blood flow that Whitehead likened to grout in a tiled wall. This defect in the "grout" makes the blood vessels dilated and leaky, causing them to break open often and bleed.
"We haven't proved that in people," he said, but "we think the same thing is happening."
The U. researchers believe that an enzyme called Rho that is responsible for sending signals to various parts of a cell causes the breakdown in the endothelium.
"At that point we started wondering how can we turn off Rho and calm this down and prevent Rho from making these blood vessels leaky," Whitehead said.
The answer -- in mice at least -- was statins such as Zocor and Lipitor, which successfully blocked the enzyme's pathway.
"When you give them to our mice, it dramatically reverses the leaking. It's all preliminary work, but we're very excited," said Whitehead, the first author of a study published Sunday in the journal Nature Medicine.
The research, he said, could have a large impact on Hispanic people in the Southwest and Rocky Mountain West who carry a gene mutation commonly passed on to them from earlier generations of their families.
University of Utah School of Medicine researchers are recruiting 50 to 100 people nationwide who are diagnosed with cerebral cavernous malformation and are on statins.
Those interested in participating a pilot trial should contact Kevin Whitehead at Kevin.whitehead@hsc.utah.edu, or Connie Lee at clee@AngiomaAlliance.org.
