An important next step in USH2c research


Erwin van Wijk (Radboudumc) has recently received a substantial grant from the Foundation Fighting Blindness USA to create a large animal model in collaboration with the research groups of Klymiuk (LMU Munich, Germany) and Ellederova & Motlik (PIGMOD Center, Libechov, Czech Republic): a USH2c pig model. This development marks a significant step towards effective treatments for patients with USH2c.

Accelerating therapy development
The grant for developing a USH2c pig model is crucial for accelerating therapy development for USH2c. This model enables the final critical studies, such as tests on the effectiveness, dosage, and toxicity of various therapies for USH2c. Currently, such studies cannot be performed with the available cell and zebrafish models for USH2c. The pig model allows researchers to take these essential last steps before therapies enter the human trial phase.

The pig eye: A valuable model
Although more alternative cell models are becoming available, it is unfortunately still not possible to develop new therapies without the use of animal models. Efforts are being made to reduce the use of animal models as much as possible, in accordance with the 3R principle: Replacement, Reduction, and Refinement. All new therapies are first extensively tested in human cell models and the previously developed USH2c zebrafish model. While these are excellent models for fundamental and translational research, they are not suitable for determining the long-term effects and safety of new treatments.
The pig eye closely resembles the human eye, both in size and morphology, and has already proven its value as a model for Usher syndrome type 1c.

A humanized USH2c model
The proposed model will be a ‘humanized’ USH2c pig model, where parts of the pig USH2C gene are replaced with the human USH2C gene, including the mutations that cause Usher syndrome. This humanized model provides the opportunity to test a wide range of current and future therapeutic strategies.

Goal and impact of the project
The main goal of this project is to generate a multifunctional humanized pig model for USH2c, in collaboration with the research groups of Nikolai Klymiuk (LMU Munich, Germany) and Jan Motlik & Zdenka Ellederova (PIGMOD Center, Libechov, Czech Republic), who specialize in generating and phenotyping pig models.
Erwin van Wijk’s research group in Nijmegen will design the pig model and produce the necessary components for its creation. In Munich, the pig will actually be created, and in the Czech Republic, a group of pigs will be bred, followed by phenotyping (analysis of vision and hearing function). Finally, various genetic analyses will be conducted in Nijmegen (at the DNA, RNA and protein levels). The project has a duration of three years.

The model is designed to determine the effectiveness of all forms of genetic therapy (RNA therapy, (mini)gene therapy, translational read-through therapy, CRISPR therapy, etc.). This model enables the translation of effective and safe therapeutic treatments from pig to human.

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