Next-Generation Sensing For Human In Vivo Pharmacology- Accelerating Drug Development In Inflammatory Diseases

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


Inflammatory diseases are responsible for significant death, disability and poor outcomes and are a major financial burden on the health service. Despite decades of research and billions of pounds of R&D investment, no targeted therapeutics exist that modulate neutrophils (a key cell involved in inflammation and also the major cell that surrounds lung cancers and promotes invasiveness and poor prognosis). Acute and chronic inflammatory diseases such as asthma, COPD and lung injury are common and are now increasing in incidence and severity due to the aging population. Hence, this research addresses, one of the biggest challenges facing modern drug development, the need to develop in-human assay systems that provide confidence in early trials to either continue progressing or terminating drug development programmes. A major cause for failures of drug development include the historical reliance on animal models of disease which do not accurately reflect human disease. It is essential to develop new technologies to understand and evaluate disease and drug effectiveness in vivo in situ in humans.

This research proposal will develop to near-clinical readiness, novel state of the art engineering and mathematical approaches to improve the quality of the data received from a sensing system called Kronoscan which is able to image and sense in real-time at microscopic detail in new dimensions using some of the world's fastest detector technology, measuring fluorescence lifetime data of inflammatory biomarkers at video rate (>10fps). Fluorescence lifetime overcomes the significant limitations of intensity fluorescence imaging and improves quantification. In patients, we will enable this through a method called microendoscopy suited to diseases that affect the lungs and gastrointestinal tracts and other areas where we can pass small imaging fibres deep into tissue. This method will be coupled alongside chemical SmartProbes which "light" up when they interact with inflamed cells and tissues.

The project will be undertaken in partnership with GlaxoSmithKline who will provide "tool" compounds in development for clinical trials. GSK already use other imaging methods such as CT Scans and PET Imaging but see this approach of adding in high resolution ultra sensitive microscopic imaging to the evaluation of drug action as a major addition to the drug development process and an essential step to improving a currently expensive and poorly productive drug development pathway.

Work on the different elements needed to create this technology platform will be undertaken by investigators spanning signal processing, electrical engineering, chemistry and clinical science at the University of Edinburgh in collaboration with GSK divisions. This project will be based in the Proteus interdisciplinary "hub" to ensure rapid product development. The researchers will spend time in each others labs in Edinburgh and GSK as well as arranging an open network meeting to ensure broader engagement. The scientists (researcher co-investigators) in the proposal will benefit significantly from networking and establishing the area of next-generation in vivo pharmacology.

A key ambition of the research will be to pave the way for subsequent clinical and commercial impact and as such user (clinical and regulatory) input will be paramount during the development of the technology. 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 drug developers, patients, doctors and health care workers throughout the world.
2) Career development of the researcher Co-Is.
3) Develop an entirely new theme with "Big Pharma".
4) A sustainable network to disseminate the technology through GSK's imaging franchise.

Planned Impact

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

Patients and Society: Inflammatory diseases are rising unabated driven by the aging population and have significant knock on effects of quality of life and productivity. The development of targeted anti-inflammatories is a "holy grail". In terms of market opportunity , the anti-inflammatory therapeutics market is expected to reach $106.1 billion by 2020, registering a CAGR of 5.9% during the forecast period 2015-2020. Although there are multiple anti-inflammatory drugs approved in the market, there is an indispensable need for better and novel anti-inflammatory therapeutics with reduced side effects and improved efficacy. The market has been driven by factors such as increasing autoimmune and respiratory conditions, new drugs in pipeline and increasing adoption of anti-inflammatory drugs. The demand for anti-inflammatory drugs has been increasing owing to the emergence of anti-inflammatory biologics (expensive intravenous antibody based drugs for arthritis) that are more targeted, effective as compared to conventional drugs.

NHS: The patient numbers with acute and chronic inflammatory diseases such as asthma, COPD, inflammatory bowel disease are large and the economic burden is enormous. The costs of complications, prolonged hospital stays, side effects from high dose systemically administered anti-inflammatories such as steroids are significant. Ultimately accelerating and refining drug development pathways to improve the developmental pathway for anti-inflammatoires, 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 engineering and physical sciences. This healthcare impact driven research programme will develop and deliver new leading-edge cross-disciplinary research in exciting and highly translatable areas of optics, chemistry and engineering . 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 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 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 be derived.

Industry: All the applicants have major interactions with industry, and most have direct personal experience of spin-off/spin-out companies. As the programme is in partnership with an industrial giant (GSK), the impact pathway is derisked. GSK are committing to developing trial strategies if the research is successful. We will have a rotating steering group that will be held biannually at GSK Stevenage.

General: The Project will benefit from close liaison with the multidisciplinary EPSRC Proteus project 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.


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Perperidis A (2020) Image computing for fibre-bundle endomicroscopy: A review. in Medical image analysis

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Taimori A (2022) Fast and Robust Single-Exponential Decay Recovery From Noisy Fluorescence Lifetime Imaging. in IEEE transactions on bio-medical engineering

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Wang Q (2020) Deep Learning in ex-vivo Lung Cancer Discrimination using Fluorescence Lifetime Endomicroscopic Images. in Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

Description The translational development of a next-generation imaging and detection system that is able to visualise and quantify molecular events deep in tissue .This system called KronoScan has been used to iterate the progression of new drugs in human lung inflammation - some of which are being developed to tackle COVID lung injury

The award also has led to the formation of a new company and strategic partnerships with major pharmaceutical companies.
Exploitation Route The software and imaging systems are being used by other parties across the UK
Sectors Digital/Communication/Information Technologies (including Software),Pharmaceuticals and Medical Biotechnology

Description A Cyber-Physical System for Unified Diagnosis and Treatment of Lung Diseases
Amount £1,083,338 (GBP)
Funding ID MR/T023252/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 05/2020 
End 04/2024
Description Baille Gifford Pandemic Science Hub: Experimental Medicine
Amount £14,700,000 (GBP)
Funding ID Baillie Gifford Pandemic Science Hub 
Organisation Baillie Gifford 
Sector Private
Country United Kingdom
Start 03/2022 
End 03/2027
Description STOPCOVID
Amount £2,000,000 (GBP)
Organisation LifeArc 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2020 
End 03/2024
Title Interventional fibre devices and imaging systems 
Description Distal lung interrogation tool for assaying alveolar tissue health 
Type Of Material Technology assay or reagent 
Year Produced 2022 
Provided To Others? Yes  
Impact Industrial engagement to develop and assess drugs in the lung in severe injury 
Description GSK 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution academic partnership - supervising PhD students
Collaborator Contribution academic partnership
Impact multidisciplinary - engineering , biology , chemistry
Start Year 2020
Description Sanofi Pasteur (SA) postdoctoral collaboration 
Organisation Sanofi
Department Sanofi Research Division
Country France 
Sector Private 
PI Contribution Collaboration part of Sanofi Pasteur Post-doctoral (PDRA) scheme with the post-doc spending one year in the university and second year in France with the company. Science mutually developed and the university post-doc conducted all the studies and performed the research under the direction of Dhaliwal with co-supervision by colleagues in Sanofi. Studies primarily focussed on T and B cell biological characterisation.
Collaborator Contribution Partner to host PDRA and access NHP facilities in France to directly compare human and NHP biology.
Impact Manuscript published - DOI: 10.3389/fimmu.2021.738955 / Abstract published - Manuscript to be submitted.
Start Year 2020