Multi Organ Functional Human On-a-Chip Systems for Drug Discovery with Focus on Efficacy
Torsten Hoffman,
,
Hesperos
It is well known that the cost of drug discovery and subsequent regulatory approval for each new candidate now exceeds $2B and in most cases requires 10-15 years of development time before general availability is granted by either the FDA or EMA. The industry would benefit greatly from better pre-clinical screening technologies for mechanistic toxicology to reduce the attrition rate during clinical trials as well as to begin to pre-select specific genetic sub-populations for optimal drug efficacy with limited distribution. A promising technology to help reduce the cost and time of this process are body-on-a-chip or human-on-a-chip systems either at the single organ level or more advanced systems where multiple organ mimics are integrated to allow organ to organ communication and interaction for mechanistic determinations for not only safety but efficacy as well. Research is now focus on the establishment of functional in vitro systems to address this deficit to create organ mimics and their subsystems to model motor control, muscle function, myelination and cognitive function, as well as cardiac subsystems are in development. The idea is to integrate microsystems fabrication technology and surface modifications with protein and cellular components, for initiating and maintaining self-assembly and growth into biologically, mechanically and electronically interactive functional multi-component systems. Cardiac systems have been developed that allow independent evaluation of electrical conduction and force generation in cardiac muscle for mechanistic studies. These have also been combined with liver systems in the same platform to include metabolic effects. Recently a 4-organ system with recirculating medium was demonstrated and multi organ toxicity that reproduced in vivo results. Overall there appears to be outstanding potential to apply these new human-on-a-chip systems to understand mechanistic toxicology and efficacy. Examples of the described technologies and systems will be presented with focus on safety and efficacy.
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