By Claire Ainsworth

At first sight, it seems like a rather perplexing experiment. In several hospitals across France, some 60 patients are taking part in a clinical trial to test a combination of three drugs. The first striking thing about this trial is that the drugs have already been approved for human use. The second is that each drug is being given at doses between 10 and 100 times weaker than those usually prescribed. Finally, and most surprising of all, none of the patients suffer from the conditions for which these drugs were originally developed. They all have Charcot-Marie-Tooth disease type 1A, a currently incurable neurological condition that causes muscle weakness and loss of touch sensation, and this trial is the result of a radically new approach to understanding and treating disease.

The approach, called network pharmacology, is very different from the current ‘targeted’ method of drug discovery. To design targeted medicines, researchers typically identify a single protein they believe causes the disease and then design a small molecule that binds exclusively to this target. Network pharmacologists take a very different tack. Rather than focusing exclusively on single proteins or individual biochemical pathways, they look at the bigger picture and target the myriad networks of interactions between the molecules in our cells.

“If we want to increase our range of potential drug targets or increase our chances of having a greater clinical effect, then we need to consider multiple modes of perturbation,” says Andrew Hopkins, who researches medicinal informatics at the University of Dundee, UK.

Network pharmacology is only a few years old but has already yielded promising results in preclinical studies, leading to new possibilities for anticancer drugs and antibiotics against multidrug-resistant bacteria. A number of human clinical trials of drugs created using network pharmacology are also underway, such as the Charcot-Marie-Tooth disease trial, which is the brainchild of the biotech company Pharnext, located just outside Paris. The disease affects one in 2,500 people, and current treatment merely manages symptoms with physiotherapy and devices such as leg braces.

Proponents say that drugs developed this way will be more effective, will have fewer side effects, and will be faster and cheaper to develop than conventional treatments because they sometimes incorporate already approved medicines. But it won’t be easy: there are large gaps in biological knowledge, and many developers are still heavily geared toward supporting the single-target, reductionist approach. “This is a difficult time for the field, which is under a lot of pressure to rapidly deliver new, safe, efficient and affordable drugs,” says Daniel Cohen, head of Pharnext. “It is hard to question the current single-target paradigm, which has probably reached its limits.

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