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light-activated dyes with antimicrobial activity able to treat chronic wound infection

An interdisciplinary research collaboration at the University of Leeds between the School of Chemistry's Colour and Polymer Science Group and the School of Biomedical Sciences led to the discovery of novel photosensitising dyes that were capable of generating singlet oxygen efficiently with (red) light of a wavelength needed for good tissue penetration. 

Summary of the impact
Leeds researchers discovered a novel class of tissue penetrating, light-activated dyes that were selectively and rapidly taken up by bacteria. Based on the dyes’ promising antimicrobial activity, the University of Leeds span-out Photopharmica in 2001; further research at Leeds has progressed the development of a targeted antimicrobial for chronic wound infections. Between 2002 and 2007 the Photopharmica raised £11.5 million in external investment; around £6.0 million has been deployed since 2009 to support a 57 patient phase IIb clinical trial. The results, which showed substantially reduced loads of all bacterial species, led to a further £0.25 million investment in 2012 to support Photopharmica’s strategy to bring an antimicrobial drug to the market.

Details of Impact
Chronic wounds such as infected leg ulcers represent a significant burden to patients and to healthcare systems throughout the world. A study in Nursing Times describes the impact of chronic wounds on a representative healthcare system: approximately 200,000 patients in the UK have a chronic wound and the cost of caring for these patients is conservatively estimated at £2.3-3.1 billion per year i.e. around 3% of total NHS expenditure. The cost of treating those patients with venous ulceration, mostly in primary care and through community nursing services, is over £168-198 million per year. Pain and odour can affect quality of life, and these common symptoms are frequently associated with poor sleep, loss of mobility and social isolation.

Health benefits – reducing infectious bacteria
Between 2009 and 2011, Photopharmica deployed around £6.0 million to fund a Phase IIb trial of antimicrobial photodynamic therapy involving PPA904 in the treatment of chronic leg ulcers. Thus, a new drug was trialled with patients. This trial involved 11 leading UK institutes and recruited 57 patients at seven sites across the UK (G). The trial showed that subjects receiving weekly PPA904 treatment (with light activation) showed a statistically greater reduction in the total load of bacteria in the wound compared to placebo and light. Crucially, significantly fewer PPA904-treated patients (compared to placebo) experienced post-treatment bacterial load levels above the recognised clinical threshold for prevention of wound healing. Significantly fewer PPA904-treated patients experienced very high post-treatment bacterial load levels, suggesting that PPA904 may reduce the risk of acquiring an infection. All bacterial species, including MRSA, were substantially and significantly reduced. The trial reported that the treatment was well tolerated and no safety concerns were raised by the independent Data Safety Monitoring Board. Analysis of wound area and quality of life scores showed that the treatment had no adverse effect on either.