In the world of cutting-edge drug discovery, organoids have already proven themselves to be a powerful way to delve deeper into human biology. They offer increasingly sophisticated models for studying diseases and are robust emerging tools for precision medicine. However, despite the many tantalizing possible applications of organoids, their current role in drug discovery is still in its infancy.
As one of the pioneers of organoid research, Robert Vries, Managing Director at Hubrecht Organoid Technology, will be delivering a presentation at our upcoming Drug Discovery 2018 conference, sharing his valuable knowledge of this exciting field. Reserve your free place here for an opportunity to attend this insightful presentation!
As a sneak peek prior to the event, Robert spoke to us about his part in developing organoids as a tool, the current status of organoids in research, and the exciting prospects of this technology in drug discovery.
Breakthroughs in organoid technology driving drug discovery
The idea of organoids is not particularly new. Since the 1980s, researchers have been exploring methods for 3D cell culturing. But it’s only recently that increased knowledge of mammalian development and tissue homeostasis, in addition to improved extracellular matrix biology, has led to current realistic in vitro models of human tissue.
One of the foremost breakthroughs occurred when scientists under the supervision of Hans Clevers found a major missing link in organoid research. “Nine years ago, we discovered for the first time the identity of adult stem cells in the intestine”, Robert explains. “Previously, we didn’t understand the regulation of stem cells in tissues, so by finding them, we could actually start our research into this area”.
Robert goes on to describe that “this was just the beginning. Later, in many other epithelia of organs such as the liver, pancreas, and more, we discovered adult stem cells and a way to expand them”. This meant that a method for growing in vitro tissue cultures of genetically stable cells that were identical to those of patients was possible. The Clevers group then used these pioneering culture protocols to model cystic fibrosis, which opened the doors to personalised treatment approaches.
The unique benefits of organoids as a drug discovery technique
One of the biggest challenges in developing models (and using those to develop drugs) is that the conventional model systems are not representative of the patients that we want to treat. Robert explains that “prior to the development of organoids, screening for drug development research would always involve the use of modified cell lines, which can be genetically unstable and may end up not resembling the original tissue. What makes organoids more realistic is not only that they’re 3D, but they come directly from patients. This allows you to create an individual model system for anyone, which you can expand indefinitely, without deviating from the original genetic or phenotypic characteristics”.
This idea could be expanded even further so that a “living biobank” or a collection of organoids from patients with various diseases could be created. The organoids in this biobank could be characterised by genome sequencing, expression profiling, and sensitivity to known drugs, to establish a database which links genetic and transcriptional information to drug responsiveness.
“From this”, says Robert “we can explore novel therapeutic strategies, including responsiveness to drug combinations, to develop rules for patient stratification based on drug sensitivity in vitro”. Traditionally, patient diversity is only introduced in the clinical stages of experimentation. With organoids, you can increase the throughput of patients in a very early and therefore affordable stage, during preclinical trials.
Overcoming the challenges associated with organoids in drug discovery
Ironically, the advantage of organoids mimicking the patient can also be a disadvantage. Their heterogeneity makes it more difficult to undertake high throughput processes in the development stage of drug discovery. In principle, they are amenable to high-throughput drug screening, but progress has been hampered by technical limitations and the extensive manipulations required by current methodologies.
As Robert explains, “currently, the screening process we’ve developed is qualified as a medium throughput system. We can screen a few tens of thousands of compounds, but not five hundred thousand compounds. That would be the next step for drug discovery”. As such, a higher throughput screening technology is sought-after.
What’s in the future for organoid technology?
A major area that organoid technology might expand into is toxicology. “Toxicology is one of these big areas where the lack of relevant models is causing a lot of problems later in the clinical studies”, Robert explains. “So, the bespoke nature of organoids could be perfectly adept at producing the relevant models”.
In addition, organoids could become a powerful tool for investigating genetic disorders. This is especially true for diseases that may not be accurately modelled in non-human species. “For example, the genetic liver disease alpha-1-antitrypsin affects young children between six and ten years old, and transplantation is needed, otherwise it’s lethal”, Robert explains. “To make a drug against this disease you need a model, but previously it was not possible to grow liver at all, let alone grow liver from these patients. With organoids, you simply take a biopsy of the transplanted livers, grow it in a lab using our culturing protocol, and obtain your model system”.
Learn more. Attend ELRIG Drug Discovery 2018 in October
If you’re keen to find out more about organoid drug discovery and would like to connect with Robert and other experts in this evolving field, book your free place at our flagship Drug Discovery 2018 conference now. Held at the Excel arena in London on October 9th and 10th, the event will allow you to explore the most recent drug discovery technology innovations, through a selection of engaging presentations and workshops delivered by world-class professionals.