Researchers from the University of
Southampton, in collaboration with researchers at the University of Quebec at
Montreal, have developed a new micro-system for more efficient testing of
pharmaceutical drugs to treat diseases such as cystic fibrosis, MG (myasthenia
gravis) and epilepsy.
A large percentage of pharmaceutical drugs
target ion channels, which are proteins found in a cell's membrane, that play a
pivotal role in these serious disorders and that are used to test the
effectiveness of new drugs.
Ion channels create tiny openings in the
membrane for specific ions (atoms that are positively or negatively charged) to
Currently researchers use
electrophysiology, which measures an electric current through ion channel
proteins, to evaluate the effectiveness of drugs on ion channels.
However, this can be a slow and expensive
process as it is typically carried out using ion channels in living cell
Quick and economical process
Now, Southampton researchers have been able
to produce an ion channel without using cells, which is possible with so-called
cell-free expression mixtures, and to insert the channels in a stable
artificial cell membrane which should enable faster, less expensive drug
testing. The key is that the cell-free expression mixture, which is known to
destabilise these membranes, can actually help with incorporating the produced
channels into a membrane between two micro droplets.
This combination of molecular biology and micro
technology transformed the conventional multi-day, multi-step single
ion-channel electrophysiology method into a quick and economical process.
"By putting the ion channel into an
artificial membrane, we only have one type of channel, no living cells and a
relatively inexpensive method for testing for several of these types of
channels at once," says lead author of the study Dr Maurits de Planque of
the Nano Research Group in Electronics and Computer Science at the University
"Researchers have experimented with
cell-free mixtures before, but they found that this method was not economical
due to the amount of expensive bio-chemicals required," adds Dr de
Planque. "Our proposal to develop a new platform, which uses a couple of
microlitres instead of millilitres, will be a very cost-effective way of doing
this, particularly when the produced channel is directly inserted in a membrane
for drug testing."
Opening up avenues
Study co-author, Biological Sciences
lecturer Dr Philip Williamson, from the University's Institute for Life
Sciences, says: "This new technology opens up avenues for drug screening,
identifying new leads and identifying off target effects. Off target effects
are a major complication in the development of new drugs, and many are
withdrawn from late stage clinical trials due to cardio-toxic effects arising
from the inhibition of the hERG voltage gated ion channel in the heart. The
hERG channel co-ordinates cardiac rhythm and the availability of cheap and
reliable assays to identify these interactions early will help streamline the
drug discovery process."