Session: Pre-Conference Workshop (SESSION CHAIR)

DAY 1: September 11, 2019 | 9:00 AM – 9:30 AM

Mechanism-Based Disease Definitions For Precision Theranostics.

Harald H.H.W. Schmidt, MD, PhD, PharmD, Maastricht University, Netherlands

Many diseases are defined by a symptom in one organ, the phenotype, not by an underlying causal mechanism, the mechanotype. Therapies are thus often not curative, but chronically reduce symptoms. In future, diseases will be defined by their mechanotype. Apart from highly penetrant monogenetic disease, most disease mechanisms involve entire signaling pathways further modulated by exposome, microbiome and behavior. Most pathways will be present in several organs; their disruption will thus most likely cause symptoms in several organs. The analysis of comorbidities will lead us to these so far unknown mechanotypes. The molecular definition of these mechanotypes i.e. the disturbance of small signaling networks is, however, not trivial. Most pathways are highly curated, e.g. KEGG, and not relevant in this form. They need to be re-established de novo in an unbiased manner. Therapies then are best based on a combination of synergistic drugs targeting different components of the same network, i.e. network pharmacology. For most targets, registered drugs are most likely available. Moreover, most drugs target in average 39 proteins, suggesting that off-target effects can be systematically exploited. To test such a causal, molecular disease mechanism, two components are essential, a mechanism-based diagnostic, which reliably detects the mechanotype, and mechanism-based drugs, i.e. a theranostic couple. This game-changing concept questions medicine’s entire current taxonomy and structure, mainly based on organs, i.e. one physician specialist and one clinic per organ and opens the door to true precision medicine.

SESSION: WELCOME MESSAGE

DAY 2: September 12, 2019 | WELCOME MESSAGE | 8:20 AM - 8:25 AM

Session 4: DRUG REPURPOSING AND NETWORK MEDICINE

DAY 3: September 13, 2019 | Session KEYNOTE | 9:20 AM – 9:50 AM

Network Medicine: The End of Medicine as We Know It?

Harald H.H.W. Schmidt, MD, PhD, PharmD, Maastricht University, Netherlands

Existing drugs often fail to provide relevant benefit for most patients. The efficacy of the discovery of new drugs is low and in a constant decline predicting that pharma will by the end of the 20’s no longer be financially sustainable and why should we eternally need to discover new drugs. This poor translational success rate of biomedical research is due to false incentives, lack of study quality and reproducibility and publication bias. Clinical research is mainly industry financed and academically rarely published. The most important reason, however, is our current concept of disease, i.e. mostly by organ or symptom, not by mechanism. Systems Medicine will lead to a mechanism-based redefinition of disease, thereby enabling precision diagnosis and therapy. Due to drug repurposing this may eventually eliminate in many cases the need for drug discovery. If successful, we may need to reorganization of how we teach, train and practice medicine, away from current organ-based disciplines, specializations and clinics and moving towards interdisciplinary board like structures. Examples of this new approach to disease include the redefinition of several cancers, immune diseases and a cluster of cerebro-cardio-metabolic phenotypes according their underlying molecular mechanism, including examples for drug repurposing and mechanism-based diagnostics.

SESSION: CONCLUDING REMARKS

DAY 3: September 13, 2019 | 4:15 PM - 4:30 PM