Patients with rare diseases: from therapeutic orphans to pioneers of personalized treatments.

Christoph Klein,William A Gahl

doi:10.15252/emmm.201708365

Abstract

Common diseases, such as cancer, diabetes mellitus, or Alzheimer9s disease, affect a large segment of the population, which justifies the enormous financial allocations for translational and clinical research. In contrast, the ~5,000 known rare disorders affect only very few patients each, even though the cumulative disease burden is substantial. This influences not only the general appreciation of research to address rare diseases, but also the allocation of research funds. Importantly, however, studying rare diseases has contributed enormously to our understanding of human biochemistry, cell and developmental biology, and physiology. For example, Linus Pauling and Vernon Ingram9s discovery of a structural difference and amino acid variant in the beta‐globin protein, which causes monogenic hemoglobinopathies such as sickle cell disease or thalassemia, issued in the era of molecular medicine (Pauling et al , 1949). Subsequently, numerous genetic defects in critical genes controlling differentiation and/or function of cells and organs have been identified and opened new possibilities for molecular diagnosis.

Highlights

“Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature, by the careful investigation of cases of rarer forms of disease
The first successful gene therapy studies were performed in patients with rare diseases, such as severe combined immunodeficiency syndromes (CavazzanaCalvo et al, 2000), factor IX deficiency (Nathwani et al, 2011), and rare genetic diseases of the retina (Bainbridge et al, 2008)
Rare disease research is fulfilling the promise of targeted therapy, that is, personalized medicine

Summary

Introduction

“Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature, by the careful investigation of cases of rarer forms of disease. Rare disease research is fulfilling the promise of targeted therapy, that is, personalized medicine. The second major challenge in rare disease research is associating a molecular diagnosis with the documented phenotype.

Results

Conclusion