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Advanced Therapies Group

The work of the group is focused on polymer therapies derived from nature in applied research.

The Advanced Therapies Group, within the School of Dentistry, is involved in using our knowledge of the molecular and cellular control of human disease processes to inform the design, development and testing of novel polymer therapeutics in the prevention and treatment of a range of difficult to treat, often life-threatening infections.

The work of the group is focused on polymer therapies derived from nature in applied research.

Aims

  • To investigate novel antimicrobial therapies, such as low molecular weight alginates and epoxytiglianes, and tailor them to optimise their maximum potential therapeutic effect against multi-drug resistant bacteria, yeasts and viruses.
  • To develop new strategies to specifically target otherwise undeliverable proteins, peptides and drugs to sites of disease by the chemical bonding of safe, water-soluble natural polymers extracted from plants and animals.
  • To characterise the antimicrobial potential of novel chronic wound dressing materials such as nanocellulose.

Key achievements

Collaborations

Low molecular weight alginates from marine algae to treat chronic respiratory disease

Industrial partnership: AlgiPharma AS, Norway

We have been involved in the development of antimicrobial and anti-biofilm polymer therapies based on a low molecular weight alginate oligosaccharide, derived from seaweed since 2007 Our subsequent research has been a key part in the optimisation of the delivery of OligoG CF-5/20 (Fig 1), as a dry powder inhalation therapy for cystic fibrosis patients (currently in Phase IIb/III clinical trials). We are extending this research as part of a multi-national collaborative research grant, we are currently looking into innovative approaches to improve drug bioavailability through more effective drug delivery, reduced toxicity, better dosing regimens and improve drug stability during translocation across the mucosal barrier (respiratory, intestinal and genito-urinary) to the target site.  This research has been funded by AlgiPharma AS, the European Social Fund, the Cystic Fibrosis Foundation and the Research Council of Norway.

Figure 1. Deposition of OligoG CF-5/20 in the CF lung. (a) Deposition of a radio-labelled OligoG CF-5/20 DPI formulation (Dry Powder for Inhalation) in the lungs of a CF patient (a) anterior and (b) posterior view. View publications. Further permissions related to the material excerpted in this figure should be directed to the ACS.

Modifying bacteria and biofilm behaviour to improve clinical wound healing outcomes using novel compounds derived from the Australian rain forest

Industrial partnership: QBiotics Ltd, Australia

We are investigating the therapeutic effect of semi-synthetic epoxytigliane compounds generated from the Blushwood tree found in the Queensland rainforest. Work by our group and our collaborators at QIMR in Brisbane, has shown that these molecules can modify the behaviour of Gram-positive multi-drug resistant (MDR) and oral pathogens, allowing diffusion through biofilm matrices and disrupting biofilms. The first in vivo studies using EBC-1013 (the lead candidate; Fig 2) have demonstrated the ability of these agents to improve the healing of chronic diabetic skin wounds. This research has been funded by Qbiotics Ltd and the Welsh Assembly Government

Figure 2. Molecular dynamics simulations (MDS) showing molecular representations of (a) EBC-1013 ligand interactions; (b) EBC-1013 embedded on the surface of the PAO1 cell outer membrane (LPS-DPPE) bilayer. (Powell et al 2021).

Polymer Conjugates

Industrial partnerships: AlgiPharma AS, Norway; Cultech Ltd, United Kingdom

The Advanced Therapies Group have proven expertise in the use of natural biodegradable polymers (e.g. polysaccharides) as novel carriers for proteins, peptides and drugs. Attachment of biodegradable polymers can improve drug targeting to sites of inflammation, thereby minimising toxicity, overcoming resistance and increasing bioavailability (Fig 3). Notably, dextrin-epidermal growth factor (EGF) conjugates developed in our group were the first polymer therapeutics for tissue repair and the first paper from this work was featured as the cover story of the Journal of Controlled Release. These pioneering studies opened up a wealth of new opportunities for bioresponsive drug delivery in tissue repair and regeneration. We have since demonstrated the benefits of using polymer conjugation for the treatment of chronic inflammation and infection, for simultaneous targeting of cancer and bacterial infections, and to support growth and differentiation of neural stem cells. In collaboration with AlgiPharma AS, we developed the first bi-functional polymer therapeutics to significantly enhance the efficacy of antibiotics. This research has been supported by collaborations with leading figures in nanomedicine and biological sciences and by highly competitive funding sources (e.g. Medical Research Council, Wellcome Trust, Royal Society, Research Council of Norway, Science and Technology Funding Council, European Social Fund (ESF) and Welsh Assembly Government).

Please see Dr Elaine Ferguson's profile for further details of current projects.

Figure 3. Schematic showing the proposed mechanism of action of polymer conjugates based on natural biodegradable polymers.

Anti-viral activity of mouthwash against COVID-19 (MOMA)

Industrial partnership: Venture Life Group PLC

Salivary spit from the mouth and throat of coronavirus patients contains a high viral load in early infection. The spread of virus by contaminated saliva is a major risk for healthcare workers caring for these patients.  Studies have shown that several mouthwashes are able to kill viruses similar to coronavirus in the mouth and throat. Laboratory tests have also indicated that certain components in mouthwashes are able to affect the coronavirus fatty “coating”. In association with Venture Life Group PLC, a clinical trial was set up to investigate if the use of mouthwash in coronavirus (COVID-19) patients can reduce the amount of virus contained within saliva. The mouthwash could be used to reduce the risk of spreading the virus to healthcare workers during a procedure involving the mouth. This research has been funded by Venture Life Group PLC.

Bacteriocin Production by Probiotic Bacteria

Industrial partnership: Cultech Ltd, Port Talbot, Wales

In association with the probiotics company Cultech Ltd, we have been investigating natural antimicrobial peptide production (bacteriocins) by probiotic lactic acid bacteria with a view to improving and optimising commercial production of mixed-population probiotics. This research has been funded by Cultech Ltd and the European Social Fund.

Current grants

Current funding (in descending financial order)

Awarding bodyDateProjectGrant

MRC New Investigator Research Grant

2016-2021

Accumulation and nephrotoxicity of dextrin-colistin conjugates

£406,496

Norwegian Research Council

2018-2022

Mucos-ALG: Development of novel alginate oligomers for enhanced delivery across mucosal barriers

£316,418

WEFO/Accelerate

Programme

2020-2022

Investigating epoxytiglianes as novel anti-biofilm therapeutics for a range of wound healing and anti-infective applications

£232,000

Sêr Cymru II Fellowship

2018-2023

The development of in vitro models of respiratory biofilm assembly to develop novel antimicrobial therapies

£165,000

QBiotics Ltd

PhD

2019-2022

Characterisation of novel epoxy-tigliane therapeutics in treatment of multi-drug resistant (MDR) wound and implant infection

£151,978

European Social Fund

KESS2 PhD

2019-2022

Developing novel technologies to model the effects of therapies on bacterial biofilms

£88,634

Venture Life Group PLC

2020-2021

Measurement of mouthwash anti-viral activity against COVID-19 (MOMA)

£73,501

Medical Research Council

2020-2021

Confidence in Concept: Potential of lactobacillus spp.-derived polysaccharides as novel bi-functional carriers in polymer conjugates

£53,468

Wellcome Trust ISSF3 Translational Kickstart award

2018-2020

Development of a nanomedicine approach for simultaneous targeting of cancer and bacterial infections

£49,645

Sêr Cymru Infrastructure accelerator award

2020-2023

Gel imaging system for multidisciplinary use in School of Dentistry, Cardiff University

£16,712

Clinical trials

Patents

Lead researcher

Professor Dave W Thomas

Professor Dave W Thomas

Professor/Hon Consultant in Oral & Maxillofacial Surgery, Programme Director Implant Dentistry, Director Wales Integrated Academic Training programme in Dentistry, School of Dentistry, URI Innovation Lead

Email
thomasdw2@cardiff.ac.uk
Telephone
+44 (0)29 207 44873

Academic staff

Dr Elaine Ferguson

Dr Elaine Ferguson

Reader in Polymer Therapeutics’

Email
fergusonel@cardiff.ac.uk
Telephone
+44 (0)2922 510663
Dr Katja Hill

Dr Katja Hill

Senior Lecturer in Oral Microbiology

Email
hillke1@cardiff.ac.uk
Telephone
+44 (0)29 2074 4252
Dr Manon Pritchard

Dr Manon Pritchard

Research Associate

Welsh speaking
Email
pritchardmf@cardiff.ac.uk
Telephone
+44 (0)29 2251 0659
Dr Lydia Powell

Dr Lydia Powell

Research Associate

Email
powelllc1@cardiff.ac.uk
Dr Saira Khan

Dr Saira Khan

Research Associate

Email
khans17@cardiff.ac.uk
Telephone
029 20745454
Nicholas Claydon

Nicholas Claydon

Senior Lecturer, Oral Biomedical Sciences

Email
claydonn1@cardiff.ac.uk
Telephone
+44 (0)29 2074 4252
Robert Adams

Robert Adams

Senior Clinical Lecturer, Oral Biomedical Sciences

Email
adamsr6@cardiff.ac.uk
Telephone
+44 (0)29 2074 4252
Joana Stokniene

Joana Stokniene

Research Associate

Email
stoknienej@cardiff.ac.uk
Dr Sian Rizzo

Dr Sian Rizzo

Research Associate

Email
rizzos3@cardiff.ac.uk

Postgraduate students

alt

Jennifer Adams

Research student

Email
adamsj23@cardiff.ac.uk
alt

Wenya Xue

Research student

Email
xuew3@cardiff.ac.uk
Telephone
+44 (0)29 2074 4252