Genetic variation and drug efficacy - could this pave the way for personalised medicines?
In this recent study published in the journal cell, researchers from the University of Copenhagen and the MRC Laboratory in Cambridge have attempted to measure the effect of genomic variations on drug pharmacodynamics. They primarily studied G-protein coupled receptors (GPCRs), the main target for most modern medicines, mapping the mutations that occur within GPCRs in individuals and investigating the impact that these mutations could have on the efficacy of medicines.
Alexander Hauser, the first author of the study, said 'We estimate that an average of 3 percent of the population have receptors that contain mutations which can alter the effect of medicine'. Madan Babu, last author of the study, added 'This might mean that the medicine simply works less efficiently. It can also mean that the medicine does not work at all or causes adverse effects on patients'.
The researchers analysed whole human genome sequencing data from the 1,000 Genomes and ExAC projects to analyse mutation in GPCRs, totalling over 60,000 participants. Using structural data they deciphered which sites were more likely to produce variations in drug response.
Alexander Hauser states that ‘The 3 percent of the affected population is an average. For some important receptors, it is way more. For instance, the relevant mutations occur in 69 percent of people in the GLP1 receptor that is the target of diabetes medicine’.
Using their data and that from GPCR targeting drug sales in the UK, they have concluded that a conservative estimate of around £14 million per year is wasted on ineffective medicines.
'The prevalence and potential impact of variation in drug response between individuals is a strong argument for further research into this field. It also constitutes a fine example of why personalised medicine might be the way forward’, says Hauser.