title: Power of rare diseases: found in translation.
abstract: Aside from established genetic evidence, the best proof of a model for disease pathogenesis rests on predicted perturbation via targeted medicines in clinical trials. Here, I discuss the strategy of performing exploratory first-in-human clinical studies on mechanistically homogeneous populations (often small groups of patients with rare diseases) as a routine entrance to full-registration clinical trials. Over the past decade, this approach has proved some pathogenic theories, disproved others, and guided investigators in new scientific directions. The immediate advantages have been smaller trials and provision of new treatments for rare diseases. Later, indications often can be expanded to subsets of more common diseases.
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA. ofrice.fishman@novartis.com
authors.forename: Mark C
authors.initials: MC
authors.lastname: Fishman
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy; D015195:Drug Design; D055808:Drug Discovery; D005260:Female; D006801:Humans; D018579:Patient Selection; D035583:Rare Diseases / Q000188:drug therapy*; D012107:Research Design; D057170:Translational Research, Biomedical / Q000379:methods* / Q000639:trends*; D014402:Tuberous Sclerosis / Q000188:drug therapy