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New genetic technique could improve drug safety in clinical trials

A new genetic technique has been developed that could lead to fewer drugs, including those for type 2 diabetes, failing the latter stages of clinical trials.
This technique has been demonstrated by the University of Cambridge (UOC) and GlaxoSmithKline (GSK), a British pharmaceutical company, and could save similar companies millions of pounds.
It involves identifying genetic variants that mimic the action of a drug on its intended target. Then these variants are checked in large patient cohorts to assess whether they are linked with health risks, such as cardiovascular disease.
Lead author Robert A Scott, Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, explained: “Genetics could soon routinely tell clinicians whether certain drugs are putting patients at risk of developing heart disease or cancer.
“[We] looked at six genes that encode the targets of various drugs for type 2 diabetes or obesity, to see whether any genetic variations were linked to metabolic traits like body mass index and fasting glucose levels.”
The researchers analysed variations in DNA encoding drug targets in almost 12,000 individuals. One of these targets was GLP1R agonists, which increase insulin production in people with type 2 diabetes and help reduce blood glucose levels.
They found a variant in the GLP1R gene that was associated with lower fasting glucose and a lower risk of type 2 diabetes. Basically, the variant appeared to mimic the action of the drug. This result was then confirmed in 40,000 more individuals.
Using genetic data, they found that the variant reduced the risk of heart disease. According to Scott, “these findings suggest that beyond their effectiveness in treating diabetes, these drugs may have the added benefit of lowering risk of heart disease.”
Pharmaceutical companies need to demonstrate a drug is effective at treating a particular condition without adverse side effects, but these effects may not be evident until late in the drug development process. By this time, millions of pounds could have been invested, but this new technique could help pharmaceuticals identify problems at an earlier stage.
“Researching and developing new medicines is a lengthy, expensive and risky journey, and any insights we can gain in to the processes of the body related to disease could help improve our ability to succeed,” says Dr Dawn Waterworth, joint senior author from GSK.
“By pooling our resources and expertise in collaborations like this one with Cambridge University, we believe there’s an opportunity to expand our knowledge of disease biology, which in turn could help reduce the risk of late-stage failures and accelerate the development of innovative new treatments for patients.”
Long-term studies investigating the cardiovascular safety of GLP1R-agonists are underway, and results from a large trial are scheduled to be released later this month.
The findings were published in the journal Science Translational Medicine.

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