DRGNET aims for less reliance on animals in pain research

The aim of the consortium project is to implement a system whereby high-quality and viable DRG neurons can be supplied to both industrial and academic researchers to increase understanding of the human sensory system and facilitate drug target identification and pharmacological testing of novel pain therapies.

Chronic pain is a common problem that affects millions of adults, impacting productivity, mobility and quality of life. Existing analgesic therapies offer either inadequate relief or intolerable side effects, including addiction. While the role of DRG neurons in pain signaling is well understood, research into more effective drug target identification has been hampered by the lack of available human DRG material in the research milieu.

The consortium aims to create an infrastructure to enable access to viable, freshly isolated human DRG. According to Metrion, “successful implementation will lead to the development of a human sensory neuronal model for improved mechanistic understanding and compound screening, which will aid in advancing the speed and quality of research into new pain therapeutics.”

By facilitating this access, immediate benefits include the replacement of the use of animal DRGs, and a reduction in the use of in-vivo exploratory programs for target identification and selection triage in favor of in-vitro models. In addition, the success of this project can lead to a reduction in the use of animals in pain research.

“[The] paradigm to reduce animal use in pain research requires the identification and validation of reliable cell and tissue surrogates, and currently the major prize in this regard is the development of human stem cell-derived iPS neurons that can approximate or fully recapitulate the properties of native (adult) human cells and tissues, such as sensory neurons of the DRG,” says Dr. Marc Rogers, chief scientific officer of Metrion.

The consortium brings together an impressive array of stakeholders interested in furthering the research towards better treatment of chronic pain. Players include the University of Glasgow, the University of St. Andrews, NHS Greater Glasgow and Clyde, the Grünenthal Group in Germany and the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), with vital support and facilitation by NHS Blood and Transplant in Scotland.

Metrion joins the Grünenthal Group as an industrial sponsor, replacing Pfizer-Neusentis in the role of evaluation and characterization of the nerve cells. The consortium project, known as DRGNET, is led by the University of Glasgow, which has received funding from the NC3Rs as part of their CRACK IT Challenges open innovation initiative.

Rogers expressed pleasure at being invited to join the consortium. “Combined with the academic and clinical credentials of the other consortium partners, we are confident of contributing to the achievement of the project goals and delivering robust in-vitro assays capable of more reliable translation of therapeutic efficacy in human pain clinical trials,” he remarked.

The DRG research offers interesting avenues for further study. Access to human DRGs may reveal “a novel pain target not previously exploited for drug discovery based on human genetics or animal testing, or reveal a significant species shift in an existing pain drug target that may affect progression and success of current candidates in preclinical testing and human clinical trials,” says Rogers.

Dr. Vicky Robinson, chief executive of NC3Rs, said: “We are delighted that Metrion has joined the DRGNET CRACK IT Challenge. The expertise and experience that Metrion brings to the Challenge in validating the human DRG neurons, in addition to that already provided by Grünenthal, is critical to the success of the program and ultimately the provision of a new resource for industry and academic scientists that allows them to reduce the use of animals in pain research and drug development.”

The intellectual property rights to the evaluation results will be owned by the University of Glasgow, and, as a sponsor, Metrion will have rights to use the data for its own research and will retain rights to any proprietary testing of compounds done within its laboratories.