Bioorthogonal Gold Chemistry to Explore Novel Biomedical Applications

Drugs used in the treatment of pain, for instance sciatica or hernia back pain, can cause serious unwanted side-effects to such a level that patients are forced to choose between symptoms (dizziness, sickness, constipation, depression) and the pain. These side effects are common in the nervous system (e.g. the brain) because they are also treatments for other conditions like anxiety and epilepsy. This unmet clinical need calls for the development of smarter medications that only work where needed, that target site of pain with no effect on the rest of the body.
To provide a safer and more effective strategy to treat localised pain, we have devised a new approach that chemically-deactivates the drugs, so they no longer have an effect. They can be reactivated with the use of gold, which would be encapsulated in a small device and implanted at the site of pain or the spine. Orally-given inactive drug precursors will only become "active" at the pain site upon interaction with the gold device, with minimal side effects. This technology is based on a novel strategy pioneered at the Edinburgh Cancer Research Centre at the University of Edinburgh that enables full control over where the therapy takes action.
In order to develop this concept, we need to first find the most effective way to deactivate the drugs, and prevent them from causing any effect, then test how quickly and efficiently they are reactivated by the gold in a biological setting. We also need to research the best way to protect the gold from attack by the body to prevent the dulling of its ability to activate the drugs over time.
Between one-third and one-half of the UK suffer from chronic pain, but this figure is expected to increase with an ageing population. Nerve pain due to sciatica and other issues including diabetes, infection and cancer, affects over 8% of the UK population. Patients suffering from multiple sclerosis, cerebral palsy, spinal cord injury and complex regional pain syndrome, for example, would be the beneficiaries of this treatment, and there is potential to expand the technology to many other chronic diseases such as Parkinson's. Due to its novelty, it will make a major impact in the pharmaceutical sector and, in turn, to the NHS and people of the UK and worldwide by improving the quality-of-life of people suffering from pain.

Impact in Healthcare. The research proposal holds potential to create a new technology delivering local pain medication without the systemic side effects that commonly cause problems. 14 million people are currently living with chronic pain, who would be potential beneficiaries of such technology. With the rise of diabetes and an ageing population, the number of people suffering from pain is expected to increase. If pain could be treated with a local medication, without the neurological side effects, the health, quality of life and well-being of those being treated would be improved. This breakthrough technology would also open the door to the development of focal treatments in other diseases, e.g. Parkinson's.
Impact on Economy. The novel IP generated from this research could eventually result in wealth creation and economic prosperity in the UK. With the realisation of the research goals, we aim to commercialise the results in the form of a spin-out company and/or attract R&D investment. Successful achievement of these goals would see the creation of jobs in the UK. Sound infrastructure exists to support commercialisation: Edinburgh Innovation (the UoE's technology office) will support IP protection and licensing; will provide advice and mentoring for the creation of spin-out companies; and links to Pharma / investors that would allow further development opportunities. Importantly, besides the University's track record in IP commercialisation, the PI has significant experience in this sector as inventor of patents for a variety of technologies and co-founder of a spin-out company. Finally, if the healthcare impacts are achieved, this technology will improve the quality of life of the patients and, in turn, creating a more productive workforce (less working days and hours would be lost to pain).