Cyber organs: Unlocking pharmacology secrets

Although these disruptive technologies have only scratched the surface of their full potential, Organs-on-a-chip are already opening up new areas of medical research.

Failure rates in clinical trials

According to a recent statement more than 60% of drugs fail in human clinical trials. Many attribute this attrition to the accuracy limitations in animal models reflecting human bio-mechanisms.

The recently published State of the Discovery Nation report emphasized the need to humanize drug discovery, so critical drug testing is performed on cell models that better represent patients.  

Biosimulation models

Many are dedicating their research to clinically relevant models that could upgrade drug discovery and potentially replace animal drug testing. This includes the likes of the organ-on-a-chip – a technology closely associated with Harvard’s Wyss Institute with Dr. Ingber as Founding Director.

Organs on a chip are representations of human organs linked by microfluidic channels on chips the size of USB sticks. The chips are preloaded with cell types designed to reflect human biology and provide a number of different readouts regarding the safety and efficacy of drug molecules. Chip equivalents of the liver, lung, heart, brain and kidney have been created.

Advances in this software will save the drug discovery community vital time, resource and money, as well as significantly reducing the number of failed trials and late stage disappointments.

Ahead of this month’s Organ on a Chip (OOAC) collaboration event between the Medicines Discovery Catapult, the Medical Research Council (MRC) Centre for Drug Safety Science (CDSS) and the National Centre for the Replacement Refinement & Reduction of Animals in Research (NC3Rs), Professor Sir Munir Pirmohamed of the MRC Centre for Drug Safety Studies at the University of Liverpool said:  “The OOAC technology will provide human data not currently available until Phase I and Phase II clinical trials that is crucial for scientists to understand both harmful and beneficial effects of drugs. It is vital that the UK becomes a leading participant to improve our ability to screen and withdraw drugs that are not viable candidates earlier in the drug development process.”

Lung on a chip

The progress of anti-influenza treatment has been hindered because animal models cannot emulate the infection mechanisms influenza viruses cause in humans.

The Wyss Institute's team is proposing to use the organ on a chip systems to overcome this barrier.

 "Virtually all existing anti-viral drugs target the virus itself, however, the ability to study influenza infection in human Lung Chips also allows us to study the host response to infection in a highly controlled way," said Dr. Ingber.

The Lung Small Airway and Alveolus Chip devices will be lined with living human lung cells that they previously showed to faithfully reproduce normal lung physiology as well as the lung diseases that impact  these regions like asthma.

"We hope to leverage this new capability to develop a new class of anti-influenza drugs that effectively make the lung tissues resistant to viral infection."

Heart on a chip

A new organ-on-a-chip device has seen success in modelling Atherosclerosis which is the leading cause of heart attacks and strokes – the constriction of blood vessels. This simulation is expected to lead to more understanding of the condition and contribute to the development of new treatments to prevent acute cardiac arrest. These inflammatory responses could not be conducted in animal models.

Limitations

In order to be true representations of the efficacy or toxicity of compounds, organs on a chip will need to account for the complex interactions between various organs in a reaction.

As a result, research is underway to connect multiple chips so they can act as a network – with the aim to achieve the prospect of a ‘human-on-a-chip’. Compounds could be tested on this digital human and then results could observe how the candidate interacts with various organs and the reactions that occur simultaneously.