Pharmacogenetics is the study of how genetic variation can lead to different responses to certain medications. Some medication may not work as effectively in some people with certain genetic changes. Some individuals may have severe reactions to their medication (called adverse drug reactions). We have been undertaking studies to see how genetic testing can be used in clinical practice to make drugs safer and more effective.
The Pharmacogenetics to Avoid Loss Of Hearing (PALOH) study is a project to assess a point of care genetic test to avoid hearing loss in neonates exposed to the antibiotic gentamicin. 90,000 babies every year in the UK are admitted or assessed on a neonatal intensive care unit (NICU). Most will receive the antibiotic gentamicin to protect against or treat infection. One in 500 babies have a genetic change called m.1555A>G which predisposes to complete irreversible hearing loss when given gentamicin. With colleagues at Genedrive we have developed a rapid test which can tell if babies are susceptible to this drug reaction in less than 30 minutes and so potentially save 200 babies every year in the UK from going deaf. This work, funded by the NIHR i4i program, is currently progressing well and we will trial the tests in Liverpool and Manchester from Summer 2019.
Genetics of Clopidogrel in patients with stroke. Clopidogrel is an antiplatelet drug that is widely used in the care of patients with coronary artery disease, vascular disease and stroke. 15% of individuals carry changes in a gene called CYP2C19 which mean that they do not respond to this drug. We are developing a study to look how rapid genetic tests of CYP2C19 can be employed to use drugs more effectively in the treatment of patients with stroke.
Genetics of in vitro fertilization (IVF) treatment:
A rare, but devastating, complication of IVF treatment is severe ovarian hyperstimulation syndrome (OHSS). This can in its most sever form be fatal or lead to women needing urgent treatment on intensive care. We believe that genetic factors may be important in this condition and are currently designing studies to determine the causes using whole genome sequencing approaches.
TARGET (TPMT: Azathioprine Response to Genotyping and Enzyme Testing)
Was a randomized controlled trial to determine if genetic testing before the use of the anti-inflammatory drug azathioprine reduced the incidence of adverse drug reactions. This was the first such study conducted in the NHS funded by the Department of Health.