What is a drug target?
And what does genetics have to do with it?
The human body does most of its work using proteins. Proteins help cells grow, send signals, and stay alive. A single human cell contains trillions of proteins, and almost half of your body weight (not counting water) is made of them. Scientists estimate that humans have just under 20,000 basic types of proteins, with many variations of each. Most medicines work by changing how one or more of these proteins behave.
To see how this works, imagine a disease where people make too much of a certain protein—we’ll call it “pretendin.” If a drug could lower the amount of pretendin in the body, then maybe the person’s symptoms would improve. If high levels of pretendin actually cause the disease, then lowering the level could greatly reduce symptoms or even cure the disease. Even if pretendin is not the original cause, it might still play an important role along the chain of events that leads to illness. Scientists call proteins like this drug targets. A drug target is typically a protein that a medicine is designed to affect. The drug might block the protein, reduce how much of it is available for the body to use, or change the protein’s shape so that it works differently. Scientists also have to think about safety, side effects, how the drug moves through the body, and how easy it is to make.
So where does genetics fit in? Most potential drugs that are tested in people never become an approved medicine. Fewer than one in ten succeed. Often this is because the drug does not actually help patients. In our example, that could happen if pretendin levels go up because of the disease, but pretendin itself is not causing the disease or the symptoms. Think of it like this: a dry sidewalk neither prevents the rain nor makes the grass brown, so wetting the sidewalk wouldn’t make it rain or help the grass. Similarly, if pretendin itself is not causing the disease or the symptoms, then changing its levels probably won’t affect the disease or its symptoms.
Genetics can help solve this problem. Genetic studies can show whether a gene—and the protein it makes—helps cause a disease, or whether the protein levels only change after the disease has already started. Drugs that target proteins with strong genetic evidence are much more likely to succeed. In fact, drugs backed by genetic evidence are estimated to be two and a half times as likely to be successfully developed as drugs without it.
One important point is that a drug can be useful even if most people do not have unusual versions of a gene. For example, some people have changes in the PCSK9 gene, which we’ve mentioned in another article, that raise their “bad” LDL cholesterol. But drugs that target the PCSK9 protein lower cholesterol in almost everyone, not just those people. That’s because the drug affects the whole protein and the biological pathway it is part of.
References:
Proteins by the Numbers | National Institute of General Medical Sciences
Refining the impact of genetic evidence on clinical success – PubMed