Combining computational and genomic data to existing drugs
The researchers, led by Dr. Atul J. Butte of Stanford University in California have reported their findings in two articles in the latest edition of ‘Science Translational Medicine. “Bringing a new drug to market usually cost around one billion dollars and many years of research and development,” said Dr. Rochelle M. Long, director of the NIH Pharmacologists Research Network, “If we can find ways to reuse drugs already approved, could improve existing treatments and save time and money.
The researchers drew their data from the Gene Expression Omnibus (National Center for Biotechnology Information), a public database containing the results of thousands of genomic studies in a wide range of fields, presented by researchers from around the world. Butte’s group focused on 100 diseases and 164 drugs, creating a computer program to search through thousands of potential drug-disease combinations, drug and disease gene whose expression patterns stalemate. For example, if a disease increases the activity of certain genes, the program tries to match it with one or more drugs that decrease this activity.
Many drug-disease combinations are known and in clinical use, supporting the validity of this approach. For example, the analysis correctly predicted that prednisolone can treat Crohn’s disease, a disease for which this medicine is a standard therapy. Other combinations are novel and surprising: a medicine to treat ulcers (cimetidine) coincided with lung cancer, and an anticonvulsant (topiramate) coincided with inflammatory bowel disease, including Crohn’s disease.
To confirm the relationship of cimetidine with lung cancer, the team tested the drug on human cells of lung cancer in the laboratory and in cells implanted in mice. In both cases, the drug slowed the growth of cancer cells compared with control cells (or mice) that did not receive cimetidine. To test whether the anticonvulsant topiramate has an effect on inflammatory bowel diseases, the researchers gave the drug to rats who had symptoms of this bowel disease: diarrhea, inflammation, ulcers and microscopic damage in the colon. The drug reduced all these symptoms, sometimes even better than prednisolone.
In addition, scientists noticed that diseases with similar molecular processes (eg, those affecting the immune system) were grouped in the analysis. So did drugs with similar effects (for example, that slow down cell division). Researchers believe that by studying the unexpected members of these groups could learn more about the progress of certain diseases and the operation of some drugs at the molecular level. According to Long, “this research is still at an early stage, but it is a promising method for a creative, fast and affordable at the time of discovering new uses for drugs already have in our armamentarium.”