Are rabbit eyes and cell models suitable?

Inherited retinal diseases, such as Usher syndrome (deafblindness), are rare conditions that result in a gradual loss of vision. These diseases have a significant impact on the quality of life of patients and their families. While most inherited retinal diseases remain largely untreatable, significant progress has been made in recent years. RNA therapies are being developed that use “genetic patches.” A major focus in the development of such therapies is the high cost associated with safety and toxicity testing of genetic patches.

One requirement that must currently be met before genetic patches can be tested in patients is that their safety—meaning that they are not toxic, harmful, or dangerous—must be demonstrated in two different vertebrate species, one of which must be a primate.

Genetic patch for each mutation
The genetic patch is specifically developed for a particular mutation or group of mutations within a gene. It has already been demonstrated in animal models and in clinical trials that genetic patches developed to mask exon 13 in the USH2A gene are safe. However, these results do not guarantee that the same will hold true for genetic patches designed for other mutations and exons. Consequently, the same tests to confirm the safety of these newly developed genetic patches must be performed. These tests are costly, time-consuming, and involve the use of many animals.

RETOX project
The “RETOX” project (Rabbit Eyes for AON-induced TOXicity evaluation), a collaboration between Radboudumc, Astherna BV, and Stichting Ushersyndroom, aims to investigate whether rabbits can be used as the sole species to rule out potential toxic reactions to genetic patches. Additionally, the project will explore whether these toxicity and safety tests can be conducted in cultured cells in the future.

If the results of the RETOX project demonstrate that rabbits are indeed suitable for determining the toxicity of genetic patches, it would significantly reduce the development costs of these therapies and decrease the number of animals used during the development of genetic patch therapies.

Read more about this study on the Health Holland website:
Suitability of rabbits and in vitro models for toxicity assessments | Health~Holland