The anti-epilepsy drug carbamazepine (Tegretol) almost doubles the risk for coronary artery disease, for example—something that wasn't known until researchers from the Brigham and Women's Hospital in Boston used computer modelling to discover side effects to 900 drugs passed as safe and effective by the US drug regulator, the Food and Drug Administration (FDA).
The modelling exposes the flaw in the one-disease, one-target approach to drug development and use: it all starts to change when the drug is introduced into our complex and inter-connected body.
Most drugs bind to a diseased protein target, but they can also interfere with unintended targets and biological processes. "The great majority of drugs are not unique to the single target for which they've been developed. They may have many off-target effects—some potentially beneficial, and some adverse," said lead researcher Joseph Loscalzo.
To discover the drugs' side effects, the researchers built a 'human protein map' based on data from 220 million patients and the impact they had specifically on coronary artery disease, where plaque build-up starts to stiffen arteries.
These unexpected side effects can explain why new drugs that show promise in animal studies fail when they are tested on people, the researchers say.
(Source: Nature Communications, 2018; 9: 2691; doi: 10.1038/s41467-018-05116-5)