Despite decades of research, disorders of the brain have proved especially difficult to treat. Consider Alzheimer’s disease. To date, every single clinical trial of a treatment for Alzheimer’s has failed to halt its progress. In January, Pfizer announced that it had ended research on drugs for it, as well as for Parkinson’s disease. Autism has been similarly frustrating. Then there is schizophrenia, which has not seen a breakthrough for more than 60 years, since the discovery of chlorpromazine (brand name: Thorazine)—which happened largely by chance.
But the story of chlorpromazine offers a powerful lesson: originally an antihistamine, it was repurposed as an antianxiety medication. That led to doctors trying it in people with pathological anxiety and in agitated psychotic patients. Finally, with a few modifications, it was reborn as an antipsychotic, ushering in a generation of medications to treat a variety of psychiatric disorders, from schizophrenia and bipolar disorder to severe depression and anxiety. These are not miracle cures, and they have serious side effects—but they are far better than what existed before.
As a neuroscientist who has studied schizophrenia for decades, I am convinced that we could have similar successes with other medicines already on our shelves, which may hold untapped promise for treating brain diseases—if only pharmaceutical companies can be prompted to share their data with scientists. Because an existing drug has already passed FDA tests to prove it is nontoxic to humans, successfully repurposing it could take less than half of the estimated 13 years and significantly less than the average $2-billion to $3-billion cost of developing a single drug from scratch. The thousands of FDA-approved drugs thus represent a vast resource that can potentially be modified to target any number of conditions. But this potential is largely unexplored, in part because companies focus on specific diseases and would have to restructure their R&D programs to look at others.
There are also thousands of drugs that are not FDA-approved, such as those stalled in clinical trials or discontinued by drugmakers. When a company abandons development of a drug, whatever researchers know is locked up in that company’s files and might as well be lost. Scientists need access to this information, and we need it now. Starting in the early 2010s, the U.S. National Institutes of Health and the U.K.’s Medical Research Council have been striking deals to take abandoned drugs from their pipelines and release that information publicly. The NIH’s National Center for Advancing Translational Sciences even provides a legal framework that lets companies protect their interests while sharing drug data. Other initiatives to create similar databases of approved and failed drugs are also under way.
If this information could be funneled into a centralized resource, along with existing data on approved drugs—and combined with the explosion in genetic knowledge related to the underlying disease mechanisms—it would be a revelation. Researchers could employ the latest tools in bioinformatics, data science and machine learning to uncover common molecular themes among or between diseases and potential drugs.
Ultimately the key is access, but many pharmaceutical companies are still reluctant to reveal anything that might jeopardize their intellectual property. Even academics may hesitate to share with competing laboratories. To remedy this, the FDA and similar entities must develop incentives for sharing data, such as by creating legal safeguards for privacy and commercial interests. These incentives could then open the floodgates for easy-to-use, open platforms for efficiently sharing and mining data. This would not have been possible five years ago. But now is a pivotal moment, and we have never been closer to real breakthroughs.
In my lab, we are testing certain cancer drugs that restore some of the biological processes that are disrupted in schizophrenia. We want to see if the drugs have the same restorative properties in the brain cells of schizophrenia patients. This is a proof of concept for the idea that a systematic and strategic approach to drug repurposing could actually move the needle. There is no time to waste. We now have the capabilities to deploy a legion of virtual researchers in search of these eureka moments. What we need is cooperation from drug companies and academic scientists alike—and access to the lifesaving data they hold.