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Glycolysis inhibition improves photodynamic therapy response rates for equine sarcoids
J P Golding1, J G Kemp-Symonds2, J M Dobson3
1School of Life, Health and Chemical Sciences, The Open University, Milton Keynes, UK.
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).
Insights
This study introduces a novel photodynamic therapy (PDT) combining 5-aminolevulinic acid (ALA) with lonidamine to enhance equine sarcoid treatment. The new method significantly improves outcomes for various sarcoid types.
Area of Science:
- Veterinary Dermatology
- Oncology
- Photochemistry
Background:
- Photodynamic therapy (PDT) is promising for skin tumors like equine sarcoids.
- Current PDT limitations include poor drug penetration and tumor antioxidant defenses.
- Lesion thickness over 2mm poses a significant challenge for effective PDT.
Purpose of the Study:
- To develop an enhanced PDT technique for equine sarcoids.
- To improve photosensitizer delivery and overcome tumor resistance.
- To evaluate the efficacy of a combination therapy for dermatological neoplasms.
Main Methods:
- Developed a transdermal penetration enhancer for topical 5-aminolevulinic acid (ALA).
- Combined ALA-PDT with topical lonidamine, a glycolysis inhibitor, post-treatment.
- Assessed treatment efficacy in vitro on sarcoid cells and in vivo on equine sarcoids.
Main Results:
- The novel PDT combination selectively killed sarcoid cells in vitro.
- Repeated treatments increased sarcoid cell sensitization to PDT.
- In vivo, ALA PDT with lonidamine achieved a 93% response rate in 27 sarcoids versus 14% for ALA-PDT alone.
Conclusions:
- This combination PDT approach significantly enhances treatment outcomes for equine sarcoids.
- The technique overcomes limitations of traditional PDT for thicker lesions.
- It offers a more effective therapeutic strategy for veterinary dermatological neoplasms.
