In the age whereby we are currently seeing a growing resistance to established drugs, and an increased pressure to design and develop new technologies and pharmaceutical agents to prevent and combat previously untreatable conditions, the industry is being pushed to develop innovative techniques in order to meet these newly set out targets.

One company, which has been established from the University of Utah, has taken up the gauntlet of the challenge and set itself a target of developing 100 hundred new drugs over the next 10 years.

Recursion Pharmaceuticals, which is a spin out of the Utah-based establishment is the brainchild of Christopher Gibson, the CEO of Recursion, who worked under the guidance of Dean Li, vice dean at the University of Utah and CSO at the University of Utah Healthcare. The company now consists of engineers and research scientists working on an innovative new disruptive model of testing drugs on diseased cells in order to uncover treatments for orphan diseases previously untreatable.

In the U.S., the Orphan Drugs Act of 1983 defines a rare disease any disease that affects less than 200,000 people in the population. There are over 7,000 conditions falling into this category affecting over 30 million Americans and less than 5% of them currently have available effective therapies. The reasons for this are two fold. The investment required from pharmaceutical companies to research and develop the therapies renders them commercially unviable. And for those diseases that do have pharmacological treatments available, the development cost is so incredibly high that it renders them out of reach of the majority of sufferers.

Gibsons’ company has embarked on an innovative mechanism by which they investigate drug candidates that have been shelved by drug companies. Their intelligent technology facilitates the tracking of cellular changes in damaged cells in order to determine changes in their physiological function, or signs of recovery. By using custom designed software they have been able to visualize these adaptations in cellular function more accurately, and to a level previously not possible.

Indeed Recursion has already demonstrated two potential therapies for Cerebral Cavernous Malformation (CCM). Through investigating the effects of the vitamin D supplement cholecalciferol as well as another pharmacological compound the research group have demonstrated a 50% reduction in lesion presentation in a mouse model. The second drug currently in pre-clinical trials seems to offer a synergistic effect when combined with cholecalciferol, and even though both compounds work separately their joint effect seems superior. Up until now the only reasonably effective solution to the pathophysiology was surgical removal of the lesion, a traumatic and highly invasive procedure.

The issues surrounding drug development are well documented. On average it takes 10-15 years to take a drug candidate through all stages of approval, and 95% of experimental compounds will end up in the freezer, not on the pharmacy shelf. Furthermore, the cost of this development process is millions and millions of dollars leaving us effectively with a commercialization process that in itself is desperately ineffective.

Conventionally the pathophysiology of a disease is studied to understand the root cause of the problem. It is only then that the incorrectly functioning mechanisms are targeted with experimental drugs, and then the testing process commences through all stages of clinical trials, finally ending with human testing to determine efficacy and safety. It is inevitable that many will fail and that the process is financially draining and inefficient.

And this is where Li’s lab has taken out many of the rate limiting steps. Rather than take the conventional approach, they have approached drug companies for their frozen failures and defrosted them to investigate as orphan drugs. They have taken the process and reversed it. Rather than using a molecule to target a disease, they have created malfunctioning cells to create a model of a human disease and then using the previously failed compounds have assessed the effects in restoring normal physiological functions. The response of the cells is a good indication of the potential of the molecule on modifying the disease state, and takes out a big step in the research process. None of their modeling processes are new as such, simply their approach, and using enhanced computerized technology, their assessment capabilities are seemingly much improved. Repurposing of drugs is not new either, however more often than not this is via good luck rather than good management and occurs out of adverse event reporting (AERs), accidental discovery and gut feeling.

At Recursion, Gibson believes that their success with CCM is replicable and scalable, and while drug repositioning may not be the ubiquitous solution to every difficult-to-manage disease, for many rare conditions he believes there is a good possibility that many previously developed drugs may be effective in diseases that are caused by loss of cellular function.