IRC Next Steps Plus: Photonic Pathogen Theranostics - Point-of-care image guided photonic therapy of bacterial and fungal infection

Lead Research Organisation: University of Edinburgh
Department Name: Centre for Inflammation Research

Abstract

Bacterial and fungal infections are responsible for significant death, disability and poor outcomes and are a major financial burden on the health service. Infections resulting from invasive procedures or injuries whereby the body's own defences are breached are common and are now increasing in incidence and severity due to the rise of antimicrobial resistance. In the past, antibiotics were readily able to treat such infections. This research thus addresses, arguably, the biggest challenge facing modern healthcare, the rise of antimicrobial resistance. The post antibiotic era is looming and novel strategies that do not rely upon conventional antibiotics and antifungals are urgently required.

This research proposal will develop to near-clinical readiness, novel classes of therapeutic molecules that will bind specifically to microbes for subsequent activation with low energy light to augment microbial killing.

Work on the different elements needed to create this technology platform will be undertaken by investigators at Edinburgh and Liverpool Universities in collaboration with partners in India and in a global surgical network. This project will be based in the Proteus interdisciplinary "hub" to ensure rapid product development. The researchers will spend time in each others labs as well as arranging an open network meeting once a year to ensure broader engagement. The scientists (researcher co-investigators) in the proposal who are all early career researchers will benefit significantly from networking and establishing the area of targeted therapeutic delivery for microbial photodynamic therapy.

The research will involve Chemists, Production Engineers, NHS Medical Physics, Bioengineers, industrial collaborators and a committed team of senior clinicians (Respiratory and Critical Care Physicians, Surgeons and Ophthalmologists) to co-develop and test the technology in a variety of model systems to demonstrate the widespread applicability in applications that involve surfaces such as the skin, wounds, eyes and in the lung. A key ambition of the research will be to pave the way for subsequent clinical development and as such user (clinical and regulatory) input will be paramount at the inception and development of the technology. The research will develop and foster global links with an ethos of "safe, affordable and scalable" solutions that will then have the highest likelihood of clinical adoption in a variety of healthcare settings. The team will leverage existing capability and expertise in manufacturing, regulatory and commercialisation support to expedite development.

In summary, this project will generate;
1) A cutting-edge point of care technology platform which will help patients, doctors and health care workers throughout the world
2) Career development of the early stage researchers
3) Sustainability for the Proteus IRC by launching into targeted therapy of infection
4) Create a sustainable network to disseminate the technology

Planned Impact

Our proposed research programme will generate numerous avenues for the realisation of impact:

Patients and Society: Antimicrobial resistance (AMR) is rising unabated driven by the widespread and indiscriminate use of antibiotics in animal and human health. Procedures, interventions and clinical care that have become routine practice and that we all, as individuals, expect to be performed safely may in the future become too dangerous to undertake because of the threat of infection and the lack of antibiotics and antifungals. For example : i) routine hip surgery may become too risky because of the possibility of infection of the prosthesis once the hip wound is closed, ii) infectious keratitis (widespread in India) may progress to blindness because of the lack of antibiotics and antifungals with efficacy, iii) care in critical care will become ever more susceptible to life threatening infections as a consequence of invasive medical devices such as endotracheal tubes for ventilation, inserted vascular and urinary catheters.

As the Chief Medical Officer of the UK has identified, AMR is the biggest threat to the population and major impact will be realised through developing this technology. Another major advance is the local and compartmental delivery of the technology to the site of the infection. Unlike systemically administered antibiotics, these activatable agents will be applied/sprayed locally to the site. This dramatically reduces the side effect profile and increases the efficacy of the therapeutic strategy.

NHS: The patient numbers undergoing invasive surgery, wound management and also care in ICUs are large and the the economic burden is enormous. The costs of complications, prolonged hospital stays, side effects from high dose systemically administered antibiotics are significant. Ultimately this will translate into reduced complications, reduced mortality and morbidity with a proportionate economic benefit.

UK PLC: UK Healthcare must reap the dividend of the current 'revolution' in physical sciences. This research programme aligned with the IRC Core will deliver new leading-edge cross-disciplinary research in exciting and highly translatable areas of optics, chemistry and targeted therapeutic delivery. Our proposed programme is driven by a clear "healthcare pull"; it fits squarely with EPSRC goals in the Healthcare and Life Sciences sector. Enabling activities through this Plus proposal will generate a globally applicable technology platform and consolidate scientists, engineers and technologists with a translational agenda and mind-set for the benefit of the UK economy and beyond.

Training: A central part of our agenda in the IRC Core is to break down traditional 'barriers' between physical and biomedical sciences. The team will benefit immensely from the interdisciplinary, translational thrust of the programme and the cross-fertilisation that will derive from the hub.

Industry: All the applicants have major interactions with industry, and most have direct personal experience of spin-off/spin-out companies. As the programme progresses new commercial opportunities will undoubtedly arise in engineering and novel chemical probes. Supported by the Core IRC, commercialization prospects in the global healthcare arena will be significant. The involvement of Aurolab which commits to developing products for ophthalmic applications from the outset in an affordable and responsible manner demonstrates a responsible route to market. BTG have also committed time to the steering group for the project.

General: The Plus Project will be part of the multidisciplinary Proteus Core and will provide many opportunities for involvement in public engagement and dissemination. The team will participate at International Science Festivals and become involved in a variety of out-reach activities and public engagement such as the 'Researchers-in-Residence Programme' placing postgraduate students in local schools.

Publications

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Long J (2020) Frugal filtering optical lenses for point-of-care diagnostics. in Biomedical optics express

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Mills B (2021) The role of fungi in fungal keratitis. in Experimental eye research

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Ucuncu M (2020) Polymyxin-based photosensitizer for the potent and selective killing of Gram-negative bacteria. in Chemical communications (Cambridge, England)

 
Description Development of a novel therapy for gram-negative bacteria photodynamic therapy agent
Development of a frugal lens for use with smartphone to detect SmartProbes
Use of SmartProbes with corneal scrapes from microbial keratitis patients
Exploitation Route The therapeutic agents maybe used as novel antimicrobials
The devices may be implementable in primary care facilities in low resource settings
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Aravind Eye Care System 
Organisation Aravind Eye Hospital
Country India 
Sector Hospitals 
PI Contribution Provision of SmartProbes and experimental protocols. Researcher time (visits). Intellectual input.
Collaborator Contribution Intellectual input. Researcher and clinician time. Equipment. Data.
Impact Research direction. New research directions. Grant applications. Joint manuscripts. Reciprocal visits. Disciplines: microbiology, immunology, engineering, chemistry, medicine, epidemiology, global health.
Start Year 2018
 
Description Point of Care Diagnostics for Microbial Keratitis - Market Entry and Technology Adoption in India 
Organisation Sathguru Management Consultants
Country India 
Sector Private 
PI Contribution We provided funding for this work through this award, in addition to research and project manager time & intellectual input
Collaborator Contribution Sathguru are a market leading consulting firm based in Hyderabad, India, and operating in the life sciences segment since 1985. They have significant experience across pharma, biotech, medtech, healthcare delivery, animal health, food and agribusiness sectors, and a particular focus on the Indian Healthcare System. They have demonstrable experience in supporting early stage healthcare technology projects with entry into the Indian Market. One of the projects within the HTAF portfolio, and one which is supported through this award, concerns the development of a point of care diagnostic device for the detection of corneal infection. Said device is intended for use in low and middle income countries (LMICs), with a particular focus on the Indian Market. The project team, and HTAF itself, sought to understand the overall market landscape in India for corneal infection detection, the key factors that will influence product adoption, the regulatory pathway for the Indian market, and to obtain support in shaping strategy for market entry in India.
Impact Sathguru provided advisory support for strategic market entry and increasing adoption of the corneal opacity detection devices. Specifically, their analysis covered the following areas/subjects: - Current landscape of devices, standard of care and unmet needs in corneal opacity detection - Assessment of customers by segment, potential for near term adoption of the innovative product - Pricing potential - Critical insights for pricing or positioning of the product - Regulatory pathway for Indian market - High level strategies for IP protection Overall analysis for recommendation on market entry strategy and key inputs for any design or functional requirements in the device for fostering higher adoption
Start Year 2019
 
Description Our Health Global 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Our Health Global is an ongoing project whereby groups of students (undergraduate and postgraduate) come together to work on a Global Health based project for ~3 months. The current Our Health Global groups are working on research questions posed by Aravind Eye Care System
Year(s) Of Engagement Activity 2019,2020