Because the drugs are already approved by the Food and Drug Administration, work done in mice could lead to clinical trials in humans in a couple of years, said Dr. Darren Browning, an associate professor and the acting graduate program director in the Department of Biochemistry and Molecular Biology at GRU.
The erectile dysfunction drugs are known as phosphodiesterase-5 inhibitors, and a variant is also used to treat pulmonary hypertension in newborns whose lungs aren’t fully formed.
“These drugs are known to be smooth muscle regulators,” Browning said.
They appear to open blood vessels by increasing cyclic GMP signaling. That cell signaling turns out to have an important role in regulating the
mucosal lining of the colon, which turns over in a regular cycle every few days and is an important barrier, he said.
If cells don’t follow the normal cycle, holes can form in the barrier, noxious things can get in and inflammation occurs that can lead to a serious infection known as colitis, Browning said.
Viagra and other drugs like it appear to strengthen that signaling to withstand that disruption, he said.
“We found we can strengthen it,” Browning said. “When the lining is subjected to some stress, we can make it more resilient using these drugs.”
Long term, that inflammation greatly increases the risk of colon cancer. Browning has a grant to study the drugs in mice in a colon cancer prevention model. But the more immediate clinical need could be treating colitis, where doctors might use drugs such as steroids that can only be used short term, Browning said.
“We have a novel way potentially of treating it,” he said. “Instead of shutting down the immune system, which is responding to a weakened barrier, we found a way to strengthen the barrier.”
Often those patients end up having part of the colon removed if no effective therapy is found. If the drugs appear to work in different mouse models of colitis, Browning hopes a clinical trial in colitis patients might begin in a couple of years.
“These patients need it now,” he said. “It’s really devastating.”