title: Glycolysis inhibition improves photodynamic therapy response rates for equine sarcoids.
abstract: Photodynamic therapy (PDT) holds great promise in treating veterinary and human dermatological neoplasms, including equine sarcoids, but is currently hindered by the amount of photosensitiser and light that can be delivered to lesions thicker than around 2 mm, and by the intrinsic antioxidant defences of tumour cells. We have developed a new PDT technique that combines an efficient transdermal penetration enhancer solution, for topical delivery of 5-aminolevulinic acid (ALA) photosensitiser, with acute topical post-PDT application of the glycolysis inhibitor lonidamine. We show that the new PDT combination treatment selectively kills sarcoid cells in vitro, with repeated rounds of treatment increasing sarcoid sensitisation to PDT. In vivo, ALA PDT followed by 600 μM lonidamine substantially improves treatment outcomes for occult, verrucous, nodular and fibroblastic sarcoids after 1 month (93% treatment response in 27 sarcoids), compared with PDT using only ALA (14% treatment response in 7 sarcoids).
authors.affiliation: School of Life, Health and Chemical Sciences, The Open University, Milton Keynes, UK.
authors.forename: J P
authors.identifier: http://orcid.org/0000-0002-7910-7382
authors.initials: JP
authors.lastname: Golding
authors.affiliation: School of Animal, Rural and Environmental Sciences, Nottingham Trent University, Southwell, UK.
authors.forename: J G
authors.initials: JG
authors.lastname: Kemp-Symonds
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Dobson
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D045744:Cell Line, Tumor; D006019:Glycolysis; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D010778:Photochemotherapy / Q000379:methods / Q000662:veterinary*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000662:veterinary*
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid
keywords: 
  PDT
  ; combination therapy; glycolysis inhibition; sarcoid; skin; tumour