IonGate Biosciences, a maker of tools that investigate transporters, and LIVC Technologies, which uses its light-induced voltage clamp technology to study voltage-induced ion channels, intend to develop and market the LIVC technology for high-throughput applications.
The resulting technology will yield robust, good quality data from the high-throughput activation and exploration of ion channels. The tool will be superior to existing methods for ion channel evaluation, including patch-clamping, because the data is more physiologically relevant, the companies said.
Ultimately, the resulting platform, which the partners hope to market by the middle of 2008, will enable researchers to screen voltage-activated ion channels in a high-throughput format, which is believed to be an improvement over currently used methods and tools for chemical and electrical depolarization.
Financial details of the agreement were not disclosed.
Wolfgang Lerch, managing director of marketing and sales for IonGate, told CBA News this week that LIVC technology uses light-activated ion channels and is based on the idea that voltage-gated ion channels are usually activated by other ion channels in order to evoke action potentials.
Lerch explained that under normal physiological conditions, a neurotransmitter activates a receptor that will activate the voltage-gated ion channels, which represent a very important class of target proteins for drug discovery, because their function is integral to the mechanism of action for therapies for many diseases.
With light-activated ion channels, it is possible to mimic normal physiological conditions in an in vitro assay system, which researchers wouldn’t have been able to accomplish using conventional technology, Lerch said.
“We use a fluorescent dye that can detect voltage changes in the membrane potential of cultured cells which contain light-activated ion channels,” Lerch told CBA News this week. “We shine light on these cells, which depolarizes them, thereby activating the voltage-gated ion channels.”
Lerch said that researchers can then use a fluorescence reader to identify test compounds as ion channel inhibitors or activators.
Faster and Cheaper
Lerch said that this method has an advantage over currently used methods for the chemical or electrical depolarization of ion channels in that “you are not using solutions that modify the cells towards unphysiological conditions, which is standard practice today.”
He pointed out that compared to currently used methods for ion channel evaluation, the LIVC technique improves data quality while reducing the time it takes to run compound library screens. The result speeds up drug discovery and reduces the cost per data point.
Bela Kelety, director of research and development for both IonGate and LIVC Technologies, said that, “Since the new system will be working without moving parts, it will be significantly faster than conventional testing.”
Existing techniques for ion channel evaluation can be divided into functional methods, such as patch-clamping, and fluorescence-based methods, said Kelety. He said that for fluorescence techniques such as LIVC, the ion channels must be activated.
Kelety said that activation of ion channels is usually accomplished by adding, for example, a potassium solution to the assay well, which depolarizes the cells, or, alternatively, using electrical stimulation with an external field.
“Both of these techniques are rather crude, however, because the whole cell is exposed to conditions that are completely different than its natural environment,” said Kelety.
The way that a cell is depolarized using light activation by LIVC is very similar to how depolarization occurs normally in vivo, Kelety said. He said that with LIVC, it is possible to switch voltage-gated ion channels on and off very quickly under physiological conditions so that researchers can stimulate the function of these ion channels in a living organism.
Kelety said that the standard methods of ion channel activation are simple, one-way experiments that are incapable of such time-dependent measurements.
IonGate and LIVC Technologies are located in Frankfurt am Main, Germany. Thiemo Gropp, a managing director of both IonGate and LIVC Technologies, said that IonGate has been working for many years with Frankfurt’s Max Planck Institute for Biophysics, one of the primary inventors of the LIVC technology.
With light-activated ion channels, it is now possible to mimic normal physiological conditions in an in vitro assay system, which is not possible using conventional technology.
IonGate originally wanted to license the technology itself, but when LIVC Technologies was founded earlier this year, decided to cooperate with the new company. Gropp said he is “basically managing director of both entities right now, so they have a very close relationship.”
“We think that the LIVC technology is very complementary to what we have now in our portfolio,” said Gropp. “We are developing transporters and high-content drug-discovery tools for transporters, and we can look at some ion channels already using our system.”
This agreement expands IonGate’s portfolio further into the ion channel field with the LIVC fluorescence-based method, Gropp said, but stressed that it is important to note that this is an emerging tool that requires further development.
According to Gropp, IonGate and LIVC have talked to several prospective partners in both the reagent and pharmaceutical fields, and will try to identify one or two well-positioned partners to work with to create a marketable product by the middle of 2008.
These partnerships will also help IonGate move aggressively into the reagent market, which is not currently the company’s main focus, Gropp said.
Gropp declined to further discuss who the prospective partners might be. “Since things are in such an early stage of development, we can just say that big pharma is very interested, but they will have to see how fast this can be brought to market as a real product that they can use in their daily work.”
According to Gropp, beta testing will begin shortly, although he did not specify a timeframe. However, he also said that both companies are confident that LIVC technology can quickly be brought to market.
IonGate will present the new technology during the “Screening Targets & Ion Channel Targets” conference in Boston on September 10.