Transfection of an Immortalized Human Cell Line to Monitor Drug Actions

MAWA Doctoral Research Scholarship

Dr Hala Raghib

Dr Hala Raghib

The inaugural MAWA Trust Doctoral Research Scholarship was awarded to Ms Hala Raghib of RMIT University in Melbourne, for a project entitled Death by QT: A New Safety Challenge.

In recent times drugs that have been in widespread use have been withdrawn from sale because they have been associated with deaths related to cardiac disturbances, the most notable example being the antihistamine terfenadine.  The safety of currently used drugs and proposed new drugs with respect to cardiac disturbances is unknown as appropriate testing, QT interval testing, is not widespread.  The genesis of the QT interval relies on the activity of cardiac ion channels responsible for action potential initiation.  Ms Raghib reported that these vary between species making the classical rodent models of testing unreliable, and currently animal experiments (for example using dogs) are recommended.  

Ms Raghib proposed an alternative approach to transfect an immortalized human cell line with the relevant human ion channels, and use this to monitor drug actions for potential cardiac disturbances.  Drugs known to affect QT in humans would then be addressed in the cell system.  This would then test the predictability of the methodology with relevance to human safety testing.  The study represented significant potential to replace animals in drug development.

Ms Raghib has now completed her doctoral project without resorting to the use of any animal products.   Professor Harry Majewski, Ms Raghib’s supervisor and Head of the School of Medical Sciences at RMIT University, stated that the result is good in that Ms Raghib now has a human cell line which has been genetically engineered with the human HERG gene without any animal methodology, even in reagents.  The MAWA Trust is pleased that this cell line is considered a useful tool and looks very promising for future research.  The second project is to investigate whether the cell line can be used to screen drugs.