Oscar Silfvergren
Modern drug discovery utilises cell- and animal-systems to predict human responses. These different systems provide different disconnected drug discovery insights and are today used for different parts in the early drug development phase. When one drug candidate development cycle ends and a transition from one system to another begins, the risk of failure is high — only 1 out of 10 candidates that enter phase 1 ends up as an approved drug. This constitutes a modern drug discovery that is expensive, slow, and due to its high dependency to animals, also ethically problematic. One potential solution is to create a translation methodology which can integrate all insights generated throughout the pre-clinical phase into an interconnected big-picture understanding, and utilise all different strengths of pre-clinical systems together. However, no such translation methodology exists to this day. Oscar’s research presents and develops such a methodology: M4 drug discovery.
M4 drug discovery presents a way to apply mono-culture cell assays, multi-culture microphysiological system (MPS) studies, and animal readouts to untreated human data for human drug predictions without human drug data. The name ‘M4 drug discovery’ stands for the insight translation across the four most critical axes: i) Multi-level insights, ranging from cellular to whole-body responses; ii) Multi-timescale insights, ranging from minutes to weeks; iii) Multi species insights, ranging from humans cells, to spheroids, rodents, monkey, dogs, and human responses; and iv) Mechanistic insights, where data-driven hypothesis testing is utilised to analyse the mechanistic underpinning of study readouts. The development of the methodology is done in a close collaboration between DMPK scientists, experimentalists, and engineers across several different companies e.g. SUND medical decisions, AstraZeneca, and Linköping university.
In the most recent years, Oscar has further developed the M4-method with additions of labelled C13 metabolites to quantify intracellular metabolic fluxes and scale such fluxes from in vitro experimental systems up to human proportions. This is done with the aim to find new ways to prevent metabolic dysregulation with potential applications in diabetes and weight change research.
Contact
E-mail: oscar.silfvergren@liu.seLinköping University profile