Computer Helps Find Possible New Uses for Old Drugs

A drug used to treat seizures might also be useful in patients with bowel diseases, while an ulcer medication may help kill lung cancer cells, two studies suggest. (Image: Marina Sirota)

Using computers to scour publicly available gene expression databases, scientists have identified new potential uses for a pair of old drugs, according to two studies published today in Science Translational Medicine.

Atul J. Butte, MD, PhD, of the Stanford University School of Medicine in Palo Alto, California, and his colleagues used a computer algorithm to search the databases for drugs that have genetic effects that are the opposite of the gene expression changes seen in patients with certain diseases. They hypothesized that drugs that countered the gene disruptions seen in such diseases would have clinical benefits. Via this high-throughput approach, the scientists identified older drugs that might be useful therapies for inflammatory bowel disease or lung cancer.

In one study, the algorithm correctly suggested that prednisolone, which is already used to treat inflammatory bowel disease, might be a useful therapy for the disorder. It also identified topiramate, a drug used to treat seizure disorders, as another potentially useful therapy. To test whether there was any validity to these findings, the scientists assessed the effects of treatment with topiramate or prednisolone compared with a placebo in mice with an inflammatory bowel disease–like disorder. They found that both drugs reduced bouts of diarrhea in the mice, but only topiramate appeared to also reduce tissue damage associated with the disease within the bowels of the treated animals.

In another study, the algorithm also suggested that cimetidine, a drug used to treat ulcers, might be a useful therapy in the treatment of lung cancer. To provide preliminary validation of this finding, the scientists tested the effects of exposure to cimetidine on lung cancer cells grown in culture and found that the drug increased cell death. Additionally, they compared the effects of cimetidine, the chemotherapy agent doxorubicin, and a control agent on tumors in mice triggered by the implantation of human lung cancer cells. They found that cimetidine was better than the placebo and at the highest dose tested was nearly as effective as doxorubicin at reducing tumor growth.

Although further studies will be necessary to validate the clinical potential of cimetidine as a lung cancer therapy and topiramate as an inflammatory bowel disease therapy, the findings provide proof-of-principle evidence that such computer-aided matching of the gene expression profiles of drugs and diseases may be helpful in identifying ways to repurpose old drugs.

In an accompanying editorial, University of Chicago scientists Yves A. Lussier, MD, and James L. Chen, MD, explain the significance of this development. They note that previous efforts had used computers to match the known mechanisms of actions of drugs with disease mechanisms, but these studies take the technology forward by incorporating “genome-wide complexity.”



Categories: Drug Therapy, Gastrointestinal Diseases, Genetics, Lung Cancer