By Aligning Databases, Scientists Match Old Drugs with New Diseases

By Veronique Greenwood | August 18, 2011 4:33 pm

pills

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:

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

  • amphiox

    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.

    And this is what robust publicly funding research is for, and why it is important.

  • http://discovermagazine.com Iain

    Americans pay more for drugs, daily, than the rest of the world, thanks to big pharma and their patents.

  • http://discovermagazine.com Iain

    To me this is an interesting side note
    If drugs can have some interesting beneficial unlooked for effects, could this not be said for un-beneficial effects unlooked for in common food additives? Doesn’t it warrant investigation?

  • Brian Too

    I thought that new uses for old drugs were patentable? In fact, I had understood that merely re-packaging or compounding old drugs also resulted in new patent opportunities?

  • Pippa

    Thanks amphiox – exactly. AND this is why it is so important that we look at our political system and ensure that large companies, including but not limited to pharma, are less able to influence political decisions. Otherwise they will continue to fund political parties and hence undermine democracy through the resulting influence that this purchases. Our politicians have to be pragmatic and vote for what is good for their sponsors, rather than what is needed for the electorate. Pharma does not want lots of publicly funded research. As a business their job is to reduce competition and maximise gains for shareholders. If we, as a people, allow the rules of politics and commerce that lead to this mess we have no one but ourselves to blame. We are, after all, still pretty much a democracy!

  • rork

    Gene Expression Omnibus (GEO) reliability varies from series to series. Some of the data sets are outstanding and famous and everything you hoped for, others are not-so-useful (perhaps small sample size or few transcripts measured), and some are not good. All hail the good people that run GEO though – it is vital for research.

    I might add that half the fun of using the other data base (I hate calling it the connectivity map) is that the top compounds you obtain might show a pattern, such as too many being antagonists of a certain pathway. (I actually want database or software to help find that pattern, since it is hard on a nerd to look at a list of compounds and have a eureka moment about where their mechanisms share some property.) It’s telling you to start looking at that pathway harder. Often you knew that already, but sometimes not.

  • Les

    Interesting and scarey. Once again, this points out that we really don’t know what all these drugs are doing in our system, yet Americans down them by the handful. Another venue the Epigenetics researchers ought to look at.

  • http://nwoodhull1@yahoo.com Nathan Woodhull

    What scares me the most is when drug companies urge doctors to write prescriptions for “off label”conditions.Doctors are now writing scripts for powerful anti-depressants for pain treatment.These drugs carry the most powerful warning called a” black box” warning and should not be allowed for any use other than what was originally intended without extensive research to uncover dammaging side effects.Unfortunately these powerful anti-depressants can also be prescribed by nurse practioners who cannot prescribe schedule two pain medications which are far less dangerous.

  • http://www.johnz.realstew.com John M. Tax

    I’m sure that many of these drugs will produce headaches, diarrhea, blurred vision, memory loss, cancer – hey just like alcohol! Let’s do more research….

    Big Pharma is not interested in cures whether patents are still in effect or not. What profit is there in one pill cures?

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