University of Tennessee researcher develops new drug therapy

Capable of suppressing disease-causing genes

The Commercial Appeal
Jul 29, 2010
By Emily Greenberg

In the near future, drug therapies might suppress genes responsible for human diseases ranging from cancers to viral infections.

Dr. John DeVincenzo, a professor and researcher at the University of Tennessee Health Science Center, designed and tested drug therapies capable of suppressing disease-causing genes in humans without altering the genes themselves. In April, the study appeared in the Proceedings of the National Academy of Sciences.

Through a process known as RNA interference (RNAi), the drug therapies suppress disease-causing genes. Although RNAi drugs showed success in test tube studies and in animals, this was the first time they were shown to successfully fight off a disease in humans.

Using computers, DeVincenzo and his team designed drug therapies to shut down the disease-causing genes.

As part of the study, DeVincenzo and his team infected 88 healthy adults with Respiratory Syncytial Virus (RSV) cultures collected and grown from patients at Le Bonheur Children's Hospital.

RSV, which has no therapy or vaccine, is the most common cause of hospitalization of infants and provides a unique opportunity to test RNAi drugs in humans, said DeVincenzo. Although RSV usually presents only mild, coldlike symptoms, it can become more serious and potentially life-threatening for infants in high-risk categories.

One challenge to testing posed by RNAi drugs is that they do not travel well through the bloodstream. Since RSV can be treated topically, the drugs could be delivered directly to the infected cells through an aerosol without having to travel through the blood stream.

In the study, half of the participants received RNAi therapy, and the other half received a placebo. Findings showed that the RNAi drugs significantly reduced infection by suppressing a gene critical to RSV.

Unlike the dangerous and currently prohibited gene therapies, the RNAi drugs do not alter a person's genes. Rather, said DeVincenzo, the drugs suppress the genes causing the disease.

As early as 2013, the drug therapy could receive approval to treat rare conditions, said DeVincenzo. Currently, DeVincenzo is conducting a clinical trial of the RNAi drugs in lung-transplant patients who were naturally infected with RSV and whose weak immune systems prevent them from fighting off the infection themselves. Eventually, DeVincenzo hopes to develop a formulation for infants, who are the most vulnerable to RSV.

Although DeVincenzo will focus his research on RSV, he says his new concept of drug design has implications for most human diseases.

"This is the biggest development in human therapeutics in about 20 years," DeVincenzo said.

-- Emily Greenberg: 529-2542