Coming soon: drugs to match your DNA

SCOTTISH doctors are building a unique gene database that will match medicines to individual patients, boosting the chances of effective treatment while reducing side-effects.

Researchers are planning to collect genetic information on 320,000 patients from blood samples taken at GPs’ surgeries.

The team at Ninewells Hospital in Dundee will use the data to unravel the genetic mysteries behind the varied reactions different people have to the same medicine.

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By examining the DNA of patients who suffer side-effects from a drug, or are responsive to it, they will pinpoint the genes responsible for the variations.

This will allow doctors to give patients a course of treatment closely tailored to their genetic make-up.

"We are looking to use genetics to improve how drugs are used," said Dr Alex Doney, a consultant vascular physician at Ninewells, and leader of the project. "The biggest problem facing doctors at the moment is that people are getting older and living longer.

"This means they are developing more and more chronic diseases like diabetes and heart disease, and are taking an increasing number of medications for a greater proportion of their lifespan.

"These medications sometimes do not do any good and can make things worse. One of the commonest reasons for hospital admissions is drug side-effects. People often stop taking drugs because of the side-effects."

Doney added: "We want to look in detail at a drug product in advance and determine when it is going to have side effects and when it is not."

Currently, doctors are forced to use trial and error to find the best drugs and work out the most effective doses when treating patients.

While a drug might benefit one patient, it might not work at all, or even have dire side-effects, in another.

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For example, the anticoagulant Warfarin is used to treat heart disease patients at risk of blood clots. While it can work well for some patients, others - even on an identical dose - can suffer severe bleeding.

In another example, Carbamazepine is highly effective at treating specific forms of epilepsy, but in rare cases it can cause a life-threatening drop in the number of white blood cells.

The reasons for such differences can depend on a variety of influences including diet, environment, and other medication being taken.

Doctors also believe there are key genes responsible for the way the body breaks down different drugs.

Doney said: "The idea is to use genetics as an extension of a person’s medical record, in the same way as cholesterol, blood pressure and blood sugar levels."

Doney and his team are planning to collect genetic information from patients in Tayside by using ‘spare blood’ left over after tests on blood samples.

He hopes the project will act as a pilot for similar pharmacogenetic databases in Scotland.

He said: "Normally the blood left over from blood samples would be discarded, but we want to keep it and link it with patients’ medical records. We estimate about 80% of the 398,000 people in Tayside will visit their doctors over the next 10 years to have a blood test."

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The opportunity to match medicines to genes - pharmacogenetics - has been made possible by the Human Genome Project, the recently-completed quest to ‘map’ every gene in the human body.

Doney said: "The great excitement about the Human Genome Project is what it can bring to medicine. The benefits are most likely to be achieved in the area of drug effectiveness."

Doctors are already using genetics to target drugs to particular patients suffering from diseases such as breast cancer.

One drug, Trastuzumab, can only be given to breast cancer patients who are found to over-express a certain hormone.

Frank Sullivan, a GP working on the project and a lecturer in clinical medicine at Dundee University, said: "As a GP I am prescribing things to people that are likely to cause side-effects, but I don’t know that in advance.

"A person may respond to one dose of a drug but not to another. If we can determine if there is a genetic explanation to this then it would take out a lot of the trial and error.

"It does not have to just apply to drugs, but also to other forms of treatment, like changes in diet, exercise and lifestyle."

But the project has also sparked alarm among some medical professionals.

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They fear pharmaceutical companies may stop producing drugs that are found to give good results in only a few patients, due to the low financial rewards.

Dr Cate Heeney, a research fellow at the ESRC Genetics Policy and Research Forum, also warned genetics may not provide all the answers on how the body interacts with medicines.

She said: "Often, while diseases have a genetic component, there are many other factors which influence it.

"Even relatively simple diseases like a cold can be very complex, so while the data from genetics will be helpful, it may not give the whole answer."

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