6 project groups take up challenges to develop animal-free innovations

The first phase of the 2023 round of Create2Solve can start with the 6 proposals selected by ZonMw to develop animal-free innovations for industry and research. The consortia will develop proof-of-concept projects for 3 of the 5 pre-formulated challenges. The project groups will have 8 months to implement their project.

Selected projects

In April this year, ZonMw published the 5 challenges from which consortia, which should be composed of at least 1 academic and 1 commercial party, could choose to collaborate on a proof-of-concept research model. From the 10 proposals submitted, ZonMw selected 6. These research consortia will now each receive a maximum of 100,000 euros. This amount does not include 'in kind' contributions from industry and/or their own institution. The research groups will now set to work to develop proof-of-concept projects on a total of 3 different challenges.

These are the projects:

Challenge 1: Development of in vitro models for drug development for arthritis:

Challenge 4: In vitro development of high-affinity antibodies

Challenge 5: Development and standardisation of complex culture methods with animal-free reagents

Follow-up

In the autumn of 2024, ZonMw will select two projects that can further develop, validate or build their animal-free innovation into a prototype in the second phase of Create2Solve. The duration of these research projects is up to 5 years.

Create2Solve: Challenging animal-free innovations

With Create2Solve, ZonMw supports the development of impactful, animal-free innovations that should lead to marketable methods, models and/or services. Funding for Create2Solve comes from the Ministry of Agriculture, Nature and Food Quality and Stichting Proefdiervrij, the Dutch Society for the Replacement of Animal Testing. Create2Solve is an initiative of the ZonMw programme More Knowledge with Fewer Animals.

Projects

Joint-on-Chip: The future of animal free drug testing in rheumatic diseases
Projectleader: Prof. Marcel Karperien (Dept. Developmental BioEngineering, Twente University)

Osteoarthritis (OA) is the most common rheumatic disease and the leading cause of mobility associated disability. OA cannot be cured as of yet. Novel treatments which showed promising results in disease modification in animal models have thus far all failed in subsequent clinical trials. Animal models for osteoarthritis are associated with severe suffering for the involved animal due to inflammation and pain responses in the joint over a prolonged period of time due to their long runway. There is an unmet need for better predictive models to test new drugs for OA. The University of Twente has invested in the development of a so-called cartilage-on-chip model which has the potential to significantly reduce the use of animal experimentation in OA drug development. The aim of this proposal is to develop this prototype cartilage-on-chip model in collaboration with the company Chiron into a marketable product for academic and industrial research programs developing new therapies for OA.
 

Human 3D synovial tissue organoids as a versatile tool to facilitate anti-rheumatic drug development for rheumatoid arthritis (3D4RA)
Projectleader: Prof. Sander Tas (Dept. Rheumatology & Clinical Immunology, Amsterdam UMC)

In this project we will develop animal-free alternatives for drug development for rheumatoid arthritis (RA). RA cannot be cured and can result in irreversible joint damage. Although RA treatment has improved tremendously, many patients do not respond adequately to current treatments. Consequently, a great unmet need for new medicines exists. Currently, animal models of arthritis are used to develop new medicines, but these models are not reliable predictors of clinical responses in humans. Moreover, these experiments cause serious animal discomfort. Therefore, a team of researchers from Amsterdam UMC, Glasgow University and AstraZeneca will develop human organoids consisting of different cell types that mimic the inflamed tissue from the joints of RA patients as closely as possible. Human organoid model systems should provide an alternate means to test the efficacy of investigational drugs for the treatment of RA, making the use of testing in animal models largely superfluous.
 

Addressing pain with Symptomatic-OA-on-Chip
Projectleader: Dr Yolande Ramos (Dept. Biomedical Data Sciences, Section Molecular Epidemiology, LUMC)

Most devastating symptom for osteoarthritis (OA) patients is pain. But frequently this is inadequately managed which has profound negative impact on both physical and mental health. Problem is that preclinical test are still performed in rodents, known to be essentially different from humans. Moreover, pain studies in animal models use behavior as a proxy for pain but lack essential quantification of sensory neuron outgrowth and activity. Better human models to test drugs to relief pain in OA are essential to advance development of safe and effective therapies.

In Phase-1, we together with AZAR Innovations will develop a Proof-of-Concept that mimics essential aspects of human OA pathophysiology including pain-sensing neurons.

In Phase-2, our concept will be further developed towards a human preclinical model fit to test drugs to treat OA-pain.
 

In vitro selection and affinity maturation of target-specific human B cells to generate animal-free high-affinity antibodies
Projectleader: Dr Gijsbert van Nierop (Dept. Viroscience, ErasmusMC)

Virus-specific antibodies are valuable tools for research, diagnostics and clinical use as immunotherapy. Classically, high-affinity antibodies are isolated from blood of repeatedly immunized laboratory animals. New technology based on recombinant antibody technology reduces the need for animals. However, major stumble blocks are identification and isolation of rare, human B cells that produce antibodies of interest and to allow affinity maturation of these antibodies.

In this proof-of-concept project we will develop a highly innovative antibody discovery pipeline based on robotic selection of virus-specific B cells with increasing affinity over time. Our aim is to mimic human germinal centers in vitro by combing contemporary primary human immune cell culture methods, highly multiplex binding and affinity screening, recombinant antibody technology and cutting-edge single cell analysis. This will be an essential step to generate high-affinity human antibodies in an animal-free manner.
 

Transition to Animal-Free Organoids (TRAFO)
Projectleader: Dr Paul Kouwer (Institute for Molecules and Materials, Radboud University Nijmegen)

Important steps in drug development can already be taken without using animals. Scientists, for example, grow mini-organs in the laboratory. However, these organoids are grown in a material derived from mouse tumors, which requires millions of animals annually, and additionally, the material has an undesirable influence on study results. Now, scientists from Radboud University and HUB Organoids (the world's leading organoid producer) are joining forces to optimize a synthetic alternative for organoid applications.

During phase 1 of our collaboration, we will optimize this synthetic gel for creating and using mini-intestines. In phase 2, we will expand its use to other organoids, develop a 100% animal-free solution, and actually bring the gel to the market through a spin-off company from Radboud University.
 

Optimization and standardization of methods required to produce serum and Matrigel free iPSC derived immune competent intestine in preparation an intra- and inter-laboratory validation study “Immuno-Gut"
Projectleader: Prof. Sue Gibbs (Dept. Molecular Cell Biology and Immunology; Amsterdam UMC)

Challenge: Development and standardisation of complex culture methods with animal-free reagents.

Major advances are being made to develop organoid platforms which will replace living animals for testing novel drugs and identifying new drug targets. An organoid is a cellular aggregate derived from stem cells which can recapitulate many of the organ functions in miniature. However, most organoids are currently dependent on Matrigel (mouse tumor extract) and Fetal Calf Serum (FCS) at some stage of the culture process.

The overall aim of Immuno-Gut is to develop methods and carry out an inter-laboratory validation study to obtain robust data for animal free production of stem cell derived intestine organoids which also contain immune cells. Phase 1 will aim to test (novel) products which do not contain Matrigel and FCS. The most promising, and where possible, totally animal-free products will be selected for further validation in an inter-laboratory study in Phase 2.