What’s the News: For all the testing we do, drugs are still mysterious things—they can activate pathways we never connected with them or twiddle the dials in some far-off part of the body. To see if drugs already FDA-approved for certain diseases could be used to treat other conditions, scientists lined up two online databases and discovered two drugs that, when tested in mice, worked against diseases they’d never been meant for, suggesting that mining of such information could be a fertile strategy for finding new treatments.
How the Heck:
- The two databases the team used were collections of information about how genes were activated or deactivated in human cells both when drugs were taken (the Connectivity Map) and when certain diseases were present (Gene Expression Omnibus).
- The researchers fed the data into software that connected a disease with a high level of activity from one gene with a drug that tamped that gene’s activity down. In this way, they identified candidates for follow up in the lab: epilepsy drug topiramate was paired with inflammatory bowel disease, and heartburn drug cimetidine with a kind of lung cancer.
- The team treated mouse models of these diseases with the drugs and observed that topiramate relieved swelling and ulcers, while cimetidine slowed lung tumor growth.
What’s the Context:
- Searching FDA-approved drug databases for effects that can be brought to bear on other illnesses isn’t that unusual in chemistry. Many scientists begin studies this way.
- But what’s nice about this study is that one of the databases, the Omnibus, is crowdsourced: researchers have been adding information to it, bit by bit, for decades, and it’s available for free. Generally, free databases that have accreted over time aren’t considered the most reliable datasets, but as this study shows, they can get the job done.
- Having the two databases pull from each other is a nice touch as well—most studies are just looking to work on a single, specific disease, but here, any combination of drug and disease is up for investigation.
Not So Fast: These particular drugs would need quite a bit more testing to see if they could be useful for these illnesses in humans. As one computational chemical biologist said to ScienceNOW, “Topiramate hits quite a lot of targets and has complex side effects, while the doses needed for functional effects for cimetidine seemed high,” though he still praised the study’s goals: “This is a really important concept; it is almost like they are looking for an antidote to a disease.”
The Future Holds: Unfortunately, through a quirk of the incentive system in pharmaceuticals, it’s unlikely that companies that first developed these drugs will invest the time and money required to test them for new uses: their patents have expired, so the companies don’t stand to profit from it. But perhaps drugs still under patent, or drugs just beginning to be tested, could be explored this way. With new drugs few and far between these days, re-purposing old ones could be a way for drug companies to fund further research.
Reference: Dudley et al. Computational Repositioning of the Anticonvulsant Topiramate for Inflammatory Bowel Disease. Science Translational Medicine. 17 August 2011: Vol. 3, Issue 96, p. 96ra76 DOI: 10.1126/scitranslmed.3002648
Sirota et al. Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data. Science Translational Medicine. 17 August 2011: Vol. 3, Issue 96, p. 96ra77. DOI: 10.1126/scitranslmed.3001318
Image credit: psyberartist / flickr