The Value of Mouse Models of Rare Diseases: A Spanish Experience

Abstract

Animal models are invaluable for biomedical research, especially in the context of rare diseases, which have a very low prevalence and are often complex. Concretely mouse models provide key information on rare disease mechanisms and therapeutic strategies that cannot be obtained by using only alternative methods, and greatly contribute to accelerate the development of new therapeutic options for rare diseases. Despite this, the use of experimental animals remains controversial. The combination of respectful management, ethical laws and transparency regarding animal experimentation contributes to improve society’s opinion about biomedical research and positively impacts on research quality, which eventually also benefits patients. Here we present examples of current advances in preclinical research in rare diseases using mouse models, together with our perspective on future directions and challenges.

Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

“…ML technology is a great opportunity for drug development as, by predicting biochemical properties of compounds and target interactions, it is possible to filter molecules with desired features while discarding others unlikely to be effective from further investigational efforts. This strategy reduces the weight of in vitro assays, animal testing and clinical trials [ 12 ], which is especially advantageous for RDs where the lack of work models and patient trials is a limiting factor [ 104 , 105 ]. A noteworthy aspect is that the performance of ML, and AI in general, intrinsically depends on the quality and completeness of the datasets used.…”

Modeling Rare Human Disorders in Mice: The Finnish Disease Heritage

“…Additionally, animal-based research often plays a crucial role in providing new insight into the understanding of diseases, associated pathologies and the identification of targets to which the treatment is directed [6]. Thus, animal experiments remain the best-but yet imperfect-model to predict and characterize human diseases [187].…”

The mouse resource at National Resource Center for Mutant Mice

“…The GEMMs for rare disease research initiative Rare diseases (RDs), the one do not yet have universal definition, refer to any disease with low prevalence, which comprise more than 7000 different conditions (Montserrat Moliner and Waligora 2013). They are usually life-threatening, chronic and clinically complex, affecting 3.5-5.9% of the world's population (Murillo-Cuesta et al 2020). With the lacking of larger enough market and economic gains, they are also known as orphan diseases, meaning difficulty to gain support and resources for discovering treatment.…”

“…Healthy and genetic monitor panels IRDiRC) have been established, with the goal of accelerating diagnosis and approving 1000 new therapies for RDs by 2027(Gahl et al 2016;Murillo-Cuesta et al 2020). NRCMM joined China Alliance for Rare Disease in 2020.…”