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NeuRoWeg – Networked innovation
NeuRoWeg – evaluating efficacy in patients through faster and more accurate test systems
“NeuRoWeg’s achievements help us to improve the R&D process and create meaningful results for patients.”
Networked innovation for a smoother drug development process
NeuRoWeg – which is the short name for the full project description “Innovative test systems for identifying curative analgesics with reliable prognosis of the effect in patients” – was recently completed. It was carried out by a regional consortium featuring academic partners and companies including Grünenthal. Conducted under the umbrella of the Leitmarktwettbewerb LifeSciences.NRW, it received funding worth € 1.5 million from the EU and the German Federal State of North Rhine-Westphalia during its three-year duration. The consortium aimed to (1) develop a more thorough mechanistic understanding of neuron-glia interactions and (2) based on these findings, generate predictive test systems to improve discovery of effective treatments for neuropathic pain in the clinic.
IPSC derived sensory neurons
A major accomplishment of NeuRoWeg achieved under the guidance of Prof. Dr. Oliver Brüstle and his team is the establishment of a standardized scalable production process for induced pluripotent stem cell (IPSC) based human sensory neurons. Showing similar characteristics as primary neurons directly isolated from either rat or human dorsal root ganglia, they are able to model human pain sensitization in the dish. Creating these IPSC-derived sensory neurons was a complex task that had posed a great challenge to science and could not be solved satisfactorily – until now. Looking forward, the protocols created by the team allow to generate sensory neurons and Schwann cells from human IPSCs in large quantities to support drug screening approaches.
Development of an innovative test system for drug screening
In addition, under the guidance of Prof. Dr. Tim Hucho, the NeuRoWeg consortium was able to develop a new High Content Screening (HCS) microscopy approach with IPSC derived sensory neurons from polyneuropathic rats and human IPSCs that monitors the response to 13 different stimuli in pain pathways at once. In this way, it is far more effective than conventional functional test systems that work with a single stimulus. This HCS approach was initially optimized in dorsal root ganglia neurons from diabetic polyneuropathic rats, where it was able to detect differences between the normal and diabetic situation and subsequently successfully transferred to human IPSC-derived sensory neurons.
“We’re proud of the consortium’s achievements. They confirm our commitment to networked research.”
NeuRoWeg – a success story
Altogether, NeuRoWeg evolved to become a very successful regional consortium project with partners from academia and industry. Grünenthal is proud of what the partners achieved together, and the consortium is currently preparing publications to share the findings of NeuRoWeg with the broader scientific community. The consortium brought together know-how of world-leading experts in the field of IPSCs and in vitro assay technologies, creating validated IPSC-derived sensory neurons which are now available as predictive tools to support Grünenthal´s research projects. The increased knowledge about pain targets and pathways is being integrated in Grünenthal’s target assessments and validations, while resilient personal contacts between the key contributors have been built. Grünenthal looks forward to leveraging new mechanistic insights and access to efficient in vitro drug screening test systems to increase the translatability from preclinic to the clinic, accelerating the R&D process and improving its success rate.
Induced Pluripotent Stem Cells (IPSC)
Induced Pluripotent Stem Cells are generated from adults’ skin or blood cells. These skin or blood cells undergo a specific induction process that transforms them into pluripotent stem cells. Pluripotent refers to these stem cell’s ability to develop into practically any cell type, including skin, nerve and muscle cells. IPSCs provide an alternative to the ethically controversial work with embryonic stem cells. They were discovered by Shinya Yamanaka in the early 2000s at Kyoto University in Japan. He was awarded with the Nobel Prize in 2012.
Sensory neurons & nociceptors
Sensory neurons, also known as afferent neurons, are neurons that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cell bodies of the sensory neurons are located in the dorsal ganglia of the spinal cord which is part of the central nervous system. A nociceptor ("pain receptor") is a sensory neuron that responds to damaging or potentially damaging stimuli by sending signals to the spinal cord and the brain. If the brain perceives the threat as credible, it creates the sensation of pain to direct attention to the body part, so the threat can hopefully be mitigated; this process is called nociception.
Mechanistic studies
A study or test designed to analyse the biologic or chemical events responsible for, or associated with, an effect observed, and to provide information concerning the molecular, cellular or physiological mechanisms by which substances exert their effects on living cells and organisms.
High Content Screening (HCS)
High Content Screening, also known as High Content Analysis (HCA), combines modern cell biology with automated high-resolution microscopy and robotic handling. This analytical method allows multi-parameter image processing and provides quantitative data from cell populations for each of the selected parameters objectively, accurately and quickly.
Acknowledgement
The project received € 1.5 million over three years from the European Funds for Regional Development and the State of North Rhine-Westphalia (Reference number EFRE-0800404).