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The chips are down

The chips are down

9 Oct 2018 by qmtbqdmdjq.d qmtbqdmdjq.d

Is it really possible to recreate a human on a chip? That is the ultimate aim of organ on a chip technology and we are getting closer. Here we explore the technology with the help of some key players

Drug discovery is challenging and suffers from high rates of failure. One limitation in drug discovery is that the preclinical cell and animal models being used lack human biological relevance.

It is vital that we explore technology that can humanise our approach to drug discovery and development.

Organ on a chip (OOAC) technology is a new approach designed to create miniaturised physiological systems suitable for drug discovery. The first aim is to create cell models that represent and mimic human organ-level functions. The OOAC technology then provides a platform to connect these organs in a plastic chip device, about the size of a USB stick, and enables communication through microfluidic channels. By developing better models, moving to 3D cell cultures and connecting these models together, OOAC provides a more relevant and patient representative testing system which will translate into better drugs and less failures during development

The OOAC system is made up of the chambers into which cell models are placed, the microfluid channels that connect these organs and a pump to circulate liquid media – mimicking the actions of a heart beat and the pressure can be increased or lowered just like blood pressure.

Professor Sir Munir Pirmohamed of the MRC Centre for Drug Safety Studies at the University of Liverpool: OOAC tech seems to have been in the offing for a while now, but we are finally at a point where it is a reality. Although still in its relative infancy, OOAC technology is gaining traction as a powerful tool for both basic and applied research. Significant, joined up research activity is ongoing in the US and across Europe – but the same is not true in the UK.

Home grown chips The UK has a strong heritage in drug discovery and established its position as a world leader by embracing innovation and new discoveries. However, SMEs account for 90% of the UK’s discovery industry and this expensive and specialist technology far outreaches their financial means. The Medicines Discovery Catapult has therefore dedicated time and resources to acquire this technology, establish and embed within the laboratories as part of its offering to the UK’s SME drug discovery community.

Dr Peter Simpson, Chief Scientific Officer of the Medicines Discovery Catapult explains: “Our role is to support these communities, whilst helping to ensure the UK remains at the heart of scientific innovation, which is why we are committed to establishing access to specialist OOAC technology here at our facility at the Medicines Discovery Catapult in Cheshire.”

As an endeavour it is the very model of an interdisciplinary undertaking. As a consequence the various pools of expertise need to come together. The National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), and others, have worked to build capacity in this area through funding of discreet projects that bring together interdisciplinary teams of industry and academic stakeholders in the development and application of OOAC models. However, greater effort is needed to build a nationwide community in this exciting space.

As a first step, the Medicines Discovery Catapult, the MRC Centre for Drug Safety Science (CDSS) and the NC3Rs, combined forces by hosting a UK OOAC event back in May this year. The event brought together the biologists, technologists, academics, regulators and funders needed to establish an OOAC community of experts within the UK.

The longer-term aim is to co-develop connected model systems that better represent human biology and make these available to UK companies. A white paper is in development that will summarise the outputs and future direction.

No more animal models? OOAC technology has the potential to be a disruptive technology for drug discovery – but could it bring a time where animal testing is removed from the pharmaceutical industry all together?

Well, It will enable drug molecules to be developed and tested in a much more patient relevant way with dynamic and interacting biology between the organs on the chip. In the short term, OOAC models will help to understand the mechanisms responsible for unexpected results observed in other systems. But as confidence in the data increases, more and more companies will start to use these devices earlier in preclinical development as part of their screening programs to inform internal decisions about what compounds to progress to the clinic based on human relevant data.

As OOAC becomes more established and accepted by the regulators we will be able to access increasingly patient relevant data that will enable us to undertake risk-free biomedical testing and reduce the need for animal disease models.

“Our aim is to drive scientific and technological developments that replace, reduce or refine the use of animals in research and to work with researchers to enable the development of tools more reflective of human biology for basic and applied science, says Dr Anthony Holmes, Director of Science and Technology at the National Centre for the Replacement Refinement & Reduction of Animals in Research. “We are incredibly proud to support the development of OOAC technology as it has the potential to not only support drug discovery but also revolutionise our approach to research.”

Chip limits It is possible to re-create and mimic many organ-level functions including those from the lungs, kidneys, heart, brain and skin. Although in most cases the complete functionality of the organ is too challenging to fully recapitulate on a chip. Particularly challenging are highly vascularised organs and those where complex structure is a pivotal part of the organ’s function – for example the kidney. Furthermore, complexities associated with neuronal networks in the brain and the connection between nerves and adjacent tissues are a work in progress. Only on the back of improved cell model systems and on chip technologies will it be possible to then integrate aspects of the immune system and hormonal regulation of cell networks.

Personalised medicine and the shift away from a one size fits all approach is an increasing trend for healthcare. Ultimately the long-term vision for OOAC technology is to develop a human on a chip. A series of 10 or more connected organs that represent the entire physiology of a patient. If this can be done, and it can be extended to use cellular material derived from patients then personalised healthcare will be a reality. This will enable specific drugs to be developed or delivered at the optimum concentrations for you as an individual. If these technologies can be scalable, then perhaps, even clinical trials on a chip may be possible.

Malcolm Haddrick