In this interview, our expert on assay development and compound profiling, Dr Paul Karila, discusses how Cellectricon’s Discovery Services are streamlining the drug discovery process within the field of CNS research.
Q) Why has Cellectricon decided to launch its Discovery Services, and how does this benefit the Pharmaceutical industry?
A) The business landscape of Pharma is changing. With recent failures and increasing costs, the Pharma industry is experiencing increased investor pressure to be more agile and cost-aware.
In light of this, Pharma companies are looking for new, more efficient ways of working, and the opportunity to outsource parts of the drug discovery process offers an accessible solution to save precious resources, including time and money. This emerging global R&D trend presented an ideal opportunity for us to offer our expertise and technology as a complete package, in the form of Discovery Services.
Another trend we have noticed is the move away from using over-expression disease models. Working instead with “disease relevant” in vitro systems provides greater insight into the disease state, and in turn a more accurate response to any effector compound.
At Cellectricon, we have expanded our offerings, so the drug discovery industry can now access the many benefits afforded by our advanced technologies as part of our Discovery Services offering.
Q) What do the Discovery Services offer and what can users expect?
A) The process of drug discovery is a risky business, and late stage attrition can incur considerable cost. By equipping customers with better decision-making information regarding compound progression, we cut the risk and avoid the cost.
Thanks to the combination of our large Drug Discovery (DDx) experience and unique technology to selectively stimulate excitable cells such as neurons and cardiomyocytes, we offer screening in disease relevant cellular and tissue models earlier. In this way, collaborators can avoid costly development of candidates without efficacy on the native target. Since we use a “phenotypic approach”, we also have the possibility to detect compounds acting along entire disease pathways, including activity toward previously unknown targets.
Q) What does Pharma gain from outsourcing?
A) As I see it, you want to outsource for two main reasons. The first reason being the access to leading expertise or technology, in an area that may lie outside the reach of internal resources. I definitely think we operate in this category, enabling Pharma companies to reduce internal risk, focus their resources and be assured of exceptional quality standards. Using an outsourcing partner also provides extra flexibility, for when you need extra capacity.
Q) What sets the Discovery Services apart?
A) In short, there are no similar technologies on the market. For excitable cells, our unique combination of expertise and proprietary technology enables us to rapidly characterize a medium-throughput screening library in disease-relevant model systems. Alternative approaches rely either upon over-expressing cell models, which provide limited biological insight, or more relevant systems that might take days to characterize a single compound.
Q) What would you say are Cellectricon’s main strengths?
A) Our knowledge in neurological diseases and DDx, in combination with our track record as developers of high-performance technological equipment is our main strength.
Research into the central nervous system is a hot topic right now, but we have yet to see many of these research findings translated “from bench to bedside”. The cytoskeleton plays a central role in neurological disease, and Cellectricon are actively exploring this by using a phenotypic approach, for added insight into the disease mechanisms.
We have particular expertise in chronic pain, and have developed a platform optimized to identify small molecule compounds affecting the sensitized dorsal root ganglion (DRG) neurons, a highly relevant model for chronic pain. This platform enables research into three main areas: selective field stimulation of excitable cells, compound delivery and transfection for genomic screening of primary cells, tissues and stem cells.
Q) How can the Discovery Services be utilized to advance research in cytoskeletal disturbances specifically?
A) The majority of the methods used today for studying drug effects on complex systems are the so-called high content imaging approaches, relying largely on fixed cell preparations. Dead tissue provides limited insight, so we use a different approach where live (neuronal) cultures play the leading role. We focus on functional responses such as neuronal excitability.
The main advantage of using excitability assays is that we can identify drug compound effects on diverse processes as ion channel synthesis, transport, insertion into the plasma membrane, or even direct action toward the ion channels. All of these effects will have an impact on overall neuronal function and therefore also on excitability.
Q) Why is the Cellaxess® Elektra Platform so suited for this work?
A) To my knowledge, our Cellaxess® Elektra Platform is the only technology with the possibility to detect excitability changes in native neuronal tissue – with a sufficient capacity to be truly enabling and decision-making.
Q) What other technology will you be using and what benefits will the different platforms bring to the Discovery Services offering?
A) Since our approach is phenotypic, we offer follow-on investigations to identify targets for active compounds. Thanks to our unique capability to selectively electroporate native neuronal tissue and other challenging cell types, we can use exactly the same test system for this, as for our excitability assay.
Q) How do you see the Discovery Services developing in the future?
A) Our goal is to develop and strengthen long-term relationships with our collaborators, which in my opinion, is the only way to truly support their on-going needs. We plan to offer a broadened portfolio of disease models, including human tissue, and will also develop our knowledge of the cytoskeleton in other CNS diseases such as Alzheimer’s disease and Parkinson’s.
Continuing to drive discoveries in CNS research, we are equipped to face whatever challenges may lie in the future.
Dr Paul Karila is Head of Discovery Services. Before joining Cellectricon in 2012, Paul was part of AstraZeneca, heading a team responsible for establishing disease-relevant in vitro models in pain research with the goal to provide “functional” target validation and compound profiling to neuropathic pain projects.
He was awarded his PhD physiology/pharmacology from Göteborg University, and pursued a postdoctoral project in neurobiology at the University of Pittsburgh, PA.