Suitability of rabbits and in vitro models for toxicity assessments
Our study will examine the option to replace higher vertebrate models in toxicity testing for lower vertebrates and/or in vitro safety assays. This will offer the promise of more efficient, cheaper, and humane advancements in the field of therapy development for retinal diseases.
Inherited retinal diseases are rare disorders that progressively affect visual function and as such, have a significant impact on the quality of life of affected individuals. Although still largely untreatable, significant progress has been made in the (pre)clinical development of RNA therapies, using “genetic patches”. A major hurdle in therapy development for rare disorders are the high costs related to preclinical safety and toxicity assessments.
Until now, clinical studies for inherited retinal diseases using genetic patches required a toxicity assessment in two species, including non-human primates. In our study, and after having obtained a positive advice from the “Commissie Beoordeling Geneesmiddelen”, we have proposed to use rabbits as alternative single species to evaluate ocular genetic patch-related toxicity. Simultaneously we will determine the predictive value of in vitro cellular assays to assess safety of the genetic patches.
The use of rabbits as a single species for toxicity assessment would reduce development costs by ~4M€ per therapeutic molecule. A potential future replacement of animal models for in vitro cellular safety and toxicity assays will even further reduce these costs by 2.5M€ per therapeutic molecule. Besides having a significant economic impact, our project also significantly contributes to the reduction, refinement and potential replacement of animal experiments.
