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‘Pharmacogenetics will become part of patient care’

Does medicine make patients feel better or worse? We are getting better at predicting this from people’s DNA profiles, says Professor Jesse Swen. ‘It never fails to fascinate me how one DNA base pair can have such a huge effect on treatment with medication and the outcome.’

Genetic variation means that patients respond differently to the same medication. Can you give a real-life example of this?

‘Three months ago, I received an email from a Canadian doctor. He explained how his brother had developed bowel cancer in his late 50s, had been prescribed medication and had died soon after.  A genetic test afterwards showed he had a certain DNA variant.

‘From our research in the Netherlands, we now know that with that DNA variant, you have to adjust the drug dosage for patients with bowel cancer. So his brother died from the drugs and not the tumour. Fortunately, this DNA test is already part of the treatment in the Netherlands.’

Drugs often don’t work as well as we would like them to. Is that the problem you are trying to solve?

‘As a hospital pharmacist and clinical pharmacologist, I spend the whole day working with drugs. We’re really pleased that they exist but we also see that they don’t always work as well as we would like them to. Drugs also cause side effects in a large number of people. There is a positive balance between the risks and the effects; otherwise drugs wouldn’t be brought to market at all. As a clinical pharmacologist, I want the right drug in the right dosage for each patient, so that it works to the max without side effects. We are by no means there yet.’

Your example of the patient with bowel cancer shows that drugs sometimes don’t work properly because of our specific DNA. When did you decide to research that?

‘It was in an elective during my pharmacy degree that I learned that genetics can affect our response to medication. That theory is nothing new. But all the technological developments and our studies at the LUMC make it possible to predict from a person’s DNA profile what effect a drug will have. In our lab, we do thousands of DNA tests on hospital patients. It never fails to fascinate me how a DNA base pair can have such a huge effect on treatment with medication and the outcome.’

You had an important publication in The Lancet in February this year, about the first study worldwide to show that prescribing drugs based on a patient’s DNA profile actually works.

‘Our research shows that if we match the dosage of a set of 39 drugs to patients’ DNA, they have a significantly lower risk of serious side effects. This is because some patients process drugs at a different speed than others, and thus require a different dose to achieve the same effect. So you need a personalised approach.

‘We used a DNA medication pass in this study that links a patient’s DNA profile to drugs whose processing is affected by DNA. By scanning this pass, doctors and pharmacists can determine the best dose for the patient.’

At the same time, you have said in previous interviews that there is still much that we don’t know. This research is just the ‘tip of the iceberg’.

‘In the Dutch pharmacogenetics working group, we have prepared specific advice for around 50 drugs on how to adjust the treatment to the patient’s DNA profile. So before starting treatment, you can do a test to avoid side effects. Research with twins also shows that we are far from being able to explain all hereditary differences in drug processing.

‘If we want to become even better at predicting the effect of DNA, we need to look at many more DNA variants in much larger groups of patients. Many non-genetic factors influence the effect of drugs. If you have an infection, for example, that affects how your body breaks down the drugs. That is something we are researching too.’

The full interview with Jess Swen was previously published on the LUMC site (in Dutch). 

His inaugural lecture ‘In Search of PharmacoPerfection’ is on Friday 17 November 2023 at 16.00. There are no more seats available but the lecture will be livestreamed too.

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