Portfolio of Cell Lines
Because of their critical roles in nerve and muscle functioning, ion channels not only influence pain, they also impact the central nervous system (CNS) and the cardiovascular system. Drugs that modulate these ion channels have therapeutic potential in many areas such as neuropathic pain, cardiac arrhythmia, hypertension, stroke, Parkinson’s disease, diabetes, and depression.
However, the lack of functional high-throughput screening technologies has limited ion channels as drug targets. To meet the growing demands for high-throughput tools to exploit ion channels, Millipore (www.millipore.com) is developing a series of ion channel cell lines useful for lead identification, profiling, and selectivity assays.
“Historically, there are two main recognized types of ion channels: voltage-gated and ligand-gated,” says Umesh Patel, Ph.D., director of the R&D ion channel group in the bioscience division of Millipore. “Voltage-gated channels open and close in response to changes in voltage. Therapeutically, this relates to cardiovascular areas as well as neuropathic pain. On the other hand, there is huge interest in ligand-gated channels because they impact the CNS and thus therapeutic areas such as insomnia, depression, epilepsy, and analgesia.”
Additionally, ion channels can be challenging to work with. “As the genes for ion channels are so large, they can be difficult for producing stable cells. It can take up to three years to make a validated cell line. We’ve built a portfolio of ion channel cell lines. Coupling these with the use of automated electrophysiology approaches has vastly accelerated throughput. In the past, one could only screen five to ten cells per day, but new instrumentation now allows screening of 384 cells simultaneously,” Dr. Patel says.
Millipore is developing assays using automated patch-clamp instruments for ion channel profiling to determine cardiac liabilities as well as improve on compound selectivity.