Repurposing and/or reactivating disused clinically relevant medical therapies

Since humans first discovered that plants and biological extracts could be used to treat ailments, many thousands of assorted therapies have been developed to treat illness and disease. In modern times these therapies include, but are not limited to, small molecule synthetic compounds, large biological proteins, and peptides. Developing new drugs and therapies is expensive, and takes a long time. Decisions about which drugs should be developed for clinical use are often made about market value and potential profit as companies seek to recoup their investment.

Over time, a considerable number of these therapies have become disused. One reason for this is due to cellular resistance, that is, the biological system that a therapy targets evolves and becomes resistant to treatment. Increasing resistance to antimicrobials, antibiotics and anti-cancer drugs is predicted to cause a global health crisis, that will return us to a medical dark-age.

In 2010 the economic impact of cancer was found be $1.16 trillion (1.5% of GDP). Cancer is difficult to treat because normal healthy cells and cancerous tumour cells are similar. This, combined with increasing anti-cancer drug resistance and the high cost of effective treatments, means that global mortality figures are only set to rise from estimated deaths of 9.6 million in 2018.

The increasing prevalence of antimicrobial resistance (AMR) in bacteria has been well advertised, however what is not so widely known is that AMR has now been identified to every antimicrobial currently marketed. By 2050 it is estimated that 10 million people per year will die from AMR diseases.

I will address this global health crisis by working to reactivate drugs that have already been approved for use but have been discarded. I will produce a technology that will revitalise currently approved medical therapies by increasing their efficacy, while simultaneously developing novel drug candidates.

To achieve this, I have invented a novel class of molecules that can stick selectively to the surface of specific types of target cell (such as cancer or bacteria). This 'sticking' process produces molecular gateways into the target cell which either result in cell death or enable drugs to pass effectively from the outside to the inside of the cell, increasing permeability of a drug towards the target cell.
This type of work is interdisciplinary, and therefore requires a team that are able to work at the interface of chemistry, biology, pharmacy and social science. Additionally, I want to find out how a team like this can be supported to create and make discoveries, and how it can work effectively.

Although currently targeted to produce novel therapeutic weapons in the fight against AMR and cancer, the development of this technology has the potential to regenerate and increase the activity for a much wider range of currently approved but disused medical therapies. It may also make drugs effective for treating a wider variety of diseases or infections where entry into the cell is the limiting factor, increasing the number and scope of illnesses that can be treated by the same drug. Therefore, this molecular innovation represents an attractive alternative to the high costs and long-timeframes associated with the conventional identification and development of a single novel drug.

Results from this study will feed directly into wider associated innovation development projects and be incorporated into quarterly development team meetings, generating instantaneous impact through informing the wider project portfolios of Co-I's and Project Partners.

SSA technology will result in the creation of novel methods towards the treatment of antimicrobial resistant (AMR) bacteria and cancer. Although drugs have been developed to treat both antimicrobial infections and cancer the dramatic increase in cellular resistance to these drugs means that many are becoming disused. In 2010 the economic impact of cancer was to decrease global Gross Domestic Profit (GDP) by $1.16 trillion (1.5% of GDP). Global mortality figures and the associated economic impacts are only set to rise from estimated deaths of 9.6 million in 2018. Similarly, by 2050 it is estimated that 10 million people per year will die from AMR diseases. Including secondary effects of AMR this is predicted to decrease GDP by $210 trillion over the next 35 years.
These infections or diseases represent the two greatest global threats to human health today and in the future. SSA innovations will simultaneously produce: i) novel therapeutic treatments and; ii) regenerate the activity of currently disused drugs towards cancer cells and AMR bacteria, where cellular permeability represents the barrier to drug efficacy. This novel approach will lower the costs associated with single molecule drug development costs, making SSA technologies affordable when licenced as therapeutic agents either as novel drugs themselves or as co-formulates for currently approved drug therapies.

Short-term impact (1-3 years):
This project provides a unique environment for the training of group members to include post-doctoral, PhD students and the Primary Investigator. This will create a highly trained UK-based people pipe-line, with the unique interdisciplinary skill set necessary to expand on SSA development within an independent academic or industrial setting. Dissemination of the initial results generated from this work at public TEAtime events, aimed at local year 10, 11, 12 and 13 students will inform the next generation of the increasing prevalence of cellular drug resistance and the associated global implications, and inspire them to become part of the solution.

Medium-term impact (4-7 years):
Experience gained from initial in-house SSA development as novel weapons in the fight against AMR and cancer, combined with our approach to open access dissemination of experimental results will self-advertise the effectiveness of this technology. This will enable us to work with the pharmaceutical industry to licence our first SSA technologies and work in partnership with drug developers to enhance the efficacy of newly developed pharmaceutical drugs that would not otherwise be considered for future development. This will result in the first SSA innovations entering clinical trials.

Long-term impact (7+ years):
SSA technologies will be licenced for use in the treatment of AMR bacterial infections and cancer. These treatments will be financially accessible due to the shared product development costs associated with this novel approach to pharmaceutical development. Use of SSAs will lower the global mortality rates associated with these infections and diseases. This will result in a comparative increase in global GDP. The researchers educated and trained during the development of these SSA technologies will make the UK a centre for the development of SSA type therapeutics, with commercial demand producing the need for spin-out companies that will provide jobs for a variety of skilled individuals and support staff.