Mechanism-based drug repurposing for (rare) diseases – Precision Medicine at its best

Precision Medicine offers great promise to advance diagnostic and treatment option for patients based on individual characteristics, profound molecular and pathway knowledge and consequently objective diagnostic means based on biomarker signatures. So far, the implementation was hampered by many factors such as current disease definitions. These are mostly symptom or organ based or an agglomeration of symptoms named after the physician who first identified the disease.

These facts render today’s disease definitions and diagnostics rather subjective and molecular basis or mechanism for the optimal treatment decision are lacking. This is a fundamental issue for drug development as many drugs target a certain set of symptom and not well-defined molecular mechanisms, therefore benefitting only subsets of patients.

Moreover, this hampers drug repurposing as precise mechanisms need to be identified to be targeted by a certain drug or compound. Mechanism-based repurposing can have a dramatic benefit as this reduces cost, time for development and renders coverage of rare diseases potentially much easier.

A key role plays an in-depth molecular characterization and biomarker signatures as well as software supported integration into the diagnostic workflow. This enables early and precise diagnosis of a disease as well as patient stratification according to their individual therapy responses and optimal doses required.

Sciomics is part of the Horizon2020 MCDS-Therapy project having the aim of repurposing Carbamazipine as a treatment for “metaphyseal chondrodysplasia type Schmid (MCDS)”, a rare bone growth disorder. An in-depth protein profiling was performed using mouse models and patient samples, comparing the model to the human situation, elucidating the molecular disease phenotype as well as identifying biomarker candidates.