The future of pain medicines:
The Leitmarktwettbewerb LifeSciences.NRW project “NeuRoWeg”
How will we test the efficacy of pain medicines in the future? An important question that we intend to answer.
“Innovative test systems for identifying curative analgesics with reliable efficacy in patients” (NeuRoWeg) is a project that was set up by our consortium following € 1.5 million of funding by the EU and the State of North Rhine-Westphalia. The project investigates the molecular basis of neuropathic pain and develops innovative new test systems that enable the efficacy of new analgesics to be assessed more accurately and rapidly. This research proposal was developed with the University Hospitals in Cologne and Bonn, and the biotech company LIFE&BRAIN.
“Our cooperative project NeuRoWeg will enhance our understanding of pain as a disease and how to cure it.”
Our aim is to improve the treatment of patients suffering from neuropathic pain – something that is presently inadequately managed by existing therapeutic agents.
We have achieved much with the collaboration within NeuRoWeg: we can adopt and optimize hands-on methods by interaction with excellent laboratories and gain much practical knowledge during colloquia and workshops with renowned experts. We strive to implement innovation beyond the “state of the art” by the joint and complementary development of improved concepts, technologies and testing methods. Grünenthal benefits form this interaction with direct access to the innovation created which can enhance our internal research.
Now, half-way into the project, it is time to summarize interim results. 18 months ago we kicked off the project aiming for the development of a high throughput screening (HTS)-compatible humanized drug discovery platform based on the translation of results from rat nerve explants. As a key result in a preclinical model of a chronic pain state, the consortium has identified by high content screening (HCS; image analysis of hundreds of cells in parallel) a previously unknow change in a cellular pathway that may give us new insights to mechanisms of chronic pain.
“The High Content Screening method as applied by the University Hospital Cologne in NeuRoWeg proved to be very efficient in the characterization of nociceptors from a preclinical in vivo model.”
Importantly, the University Hospital Bonn and LIFE&BRAIN have successfully established a robust pipeline for the generation and distribution of highly mature human induced pluripotent stem cell (iPSC)-derived nociceptors for direct functional and image-based analysis in a miniaturized format (96-well plates). Basic electrophysiological assessment of the iPSC-derived nociceptors revealed a remarkable resemblance to human and rat DRG explants. To eventually model the contribution of neuron-glia cross talk in neuropathic pain etiology and persistence, partners have established a method for the derivation of iPSC-derived Schwann cells. With the vision to mimic the human physiology and pathology of axoglial interactions in neuropathic pain, we and partners have now started to also assess the functional properties of iPSC-derived Schwann cells with regard to their electrophysiological characteristics and myelination potential in vitro. In summary, the consortium expects to advance pain research and drug discovery by delivering innovative technologies and methods for the establishment of a humanized HCS-platform.
“We are always looking for innovative test systems that enable us to quickly and reliably predict if new drugs will be effective in humans.”
Human pluripotent stem cells are unique and powerful tools for bridging the predictive gap from our accumulated knowledge of animal models to human therapy development. Combining the expertise of lead scientists and renowned specialists in stem cell technologies and pain signaling, we are working to develop a humanized drug screening platform employing the power of pluripotent stem cells and image-based HTS-compatible assay development. The successful implementation of such a platform opens up the opportunity to identify innovative pain medications to cure patients.
Our aim is to improve the treatment of patients suffering from neuropathic pain – something that is presently inadequately managed by existing therapeutic agents. We achieved so much with the collaboration within NeuRoWeg: we can adopt and optimize hands-on methods by interaction with excellent laboratories, and gain much practical knowledge during colloquia and workshops with renowned experts. We strive to implement innovation beyond the “state of the art” by the joint and complementary development of improved concepts, technologies and testing methods. For the complete running time of the collaboration, there is an additional laboratory technician employed. This progress will open up the opportunity for Grünenthal to receive maturated neuronal iPSC-derived sensory neurons for our preclinical testing – for an improved predictivity of effects in humans.
“After my apprenticeship here at Grünenthal, I had the chance to work for the NeuRoWeg project. Especially through the cooperation with the external partners, I was able to learn a variety of new methods and to establish them in our lab. For my professional and personal development, the participation in this project is of highest benefit.”
This progress will open up the opportunity for Grünenthal to receive maturated neuronal iPSC-derived sensory neurons for our preclinical testing – for an improved predictivity of effects in humans.
“In the NeuRoWeg consortium generated nociceptors from stem cells. These are astonishingly similar in function and expression to those we isolate from human dorsal root ganglia.”
In 2015, the State of North Rhine-Westphalia set up competitive granting body, LifeSciences.NRW to support the development of health and welfare solutions for an aging population. A consortium of academic institutions, small and mid-sized enterprises and pharmaceutical companies in NRW were offered the chance to compete for financial support from the European fund for regional development for innovative biomedical research and development projects. The intention is to strengthen growth and employment in NRW and increase its visibility as a global hub for life sciences.
To find out more visit https://www.leitmarktagentur.nrw/leitmarktwettbewerbe/lifesciences