Metabolomics for Animal Models of Rare Human Diseases: An Expert Review and Lessons Learned.

ABSTRACT

Rare diseases occur with a frequency ≤11500-12500 depending on the location and applicable definitions across countries. Although individually rare, they collectively affect as much as 4-8% of population imposing a large burden on public health. Rarity in prevalence means prolonged path to accurate diagnosis, lack of treatment options, and also limited chances for preclinical studies of pathogenesis. I discuss in this expert review (1) what metabolomics, as a high throughput systems sciences technology, offers for rare disease studies, (2) why animal models are important for the study of rare human diseases and what should be kept in mind while using animal models, and finally, (3) provide examples of recent research to highlight how metabolomics on animal models of rare diseases perform, and how these results can lead to the knowhow, which raises genome, metabolome, and phenotype integration to a whole new level. In sum, metabolomics has been for years in clinical use for diagnosis of certain types of rare diseases. Determination of pathogenesis of more complex diseases and testing of treatment strategies is where animal models and systems biology analytical approaches are necessary. From gathered data, it is possible to go back to diagnostic and prognostic markers for rare diseases, which so far lack reliable and robust diagnosis and therapeutic options. In the future, a major challenge is to reveal the links between genotype, metabolism, and phenotype. Rare diseases could be the key in that process.