Discovery of biomarkers in rare diseases: innovative approaches by predictive and personalized medicine

Abstract

There are more than 8000 rare diseases (RDs) that affect >5 % of the world’s population. Many of the RDs have no effective treatment and lack of knowledge creates delayed diagnosis making management difficult. The emerging concept of the personalized medicine allows for early screening, diagnosis, and individualized treatment of human diseases. In this context, the discovery of biomarkers in RDs will be of prime importance to enable timely prevention and effective treatment. Since 80 % of RDs are of genetic origin, identification of new genes and causative mutations become valuable biomarkers. Furthermore, dynamic markers such as expressed genes, metabolites, and proteins are also very important to follow prognosis and response the therapy. Recent advances in omics technologies and their use in combination can define pathophysiological pathways that can be drug targets. Biomarker discovery and their use in diagnosis in RDs is a major pillar in RD research.

Belgian rare diseases plan in clinical pathology: identification of key biochemical diagnostic tests and establishment of reference laboratories and financing conditions

“…Using those criteria, 73 priority analyses were selected for coverage in the following elds: clinical chemistry (46), coagulation and hemostasis (11), immuno-haematology and non-infectious serology (9), hormonology (4), and haematology (3) (cf. Figure 2).…”

“…Because most of rare diseases have a genetic origin, the Belgian centers of human genetics were rstly involved in the process, followed by a speci c action focused on biochemical laboratory tests performed by medical laboratories. Indeed, genetic and biochemical tests are highly complementary in order to investigate and follow rare diseases' mechanisms, the underlying biochemistry, cellular pathways and response to treatments (11).…”

Clinical Trials and the Importance of Biobanks in Rare Diseases

“…The "omic" technologies in RDs make possible genome analysis, determination of proteins and metabolites profiles in a particular tissue / cell, detection of diagnostic and therapeutic biomarkers. 28 Based on the aforementioned, biobanks for RDs are facing with a number of challenges, additionally to required quality of biological material. In the future there must be developed system that will connect with patient registers and their clinical data to facilitate location and exchange of research samples, and secure patient privacy in accordance according to ethical and legal provisions in different countries.…”

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

“…The exact number of how many rare diseases exist remains obscure but it likely ranges from 5000 to 10,000, with the higher end probably being closer to the truth (Ferreira, 2019). All together these thousands of individually rare diseases affect 4-8% of the population, although the number is only an estimate because it is hard to keep track of diseases that evade diagnosis (Ferreira, 2019;Gulbakan et al, 2016).…”

“…Screening for inborn errors of metabolism, which all are rare diseases, has been part of national health care since the late 1990s and the list of countries doing so is continuously growing (Fabie et al, 2019;Therrell and Padilla, 2018;Wilcken et al, 2003). Today when metabolomics has proven its value for diagnosis and also revealed its weak sides, the initiative is to apply it on all rare and undiagnosed diseases (Crowther et al, 2018;Gulbakan et al, 2016;Ramoni et al, 2017). The aim was to speed up diagnosis and treatment strategies for all rare diseases.…”