The plant defensin HXP124 has the potential to be a new safe and effective topical treatment for onychomycosis 

Objectives: Plant defensins with potent antifungal activity have the potential to be developed as effective and robust treatments for fungal infections in humans.  The cysteine-stabilised structure of plant defensin’s makes them extremely stable and able to withstand extremes of pH and temperature. Here we investigate the antifungal properties of a novel plant defensin, HXP124, against a range of clinically important fungal pathogens. HXP124 has potent antifungal activity against a range of human fungal pathogens including Candida spp, Cryptococcus spp, dermatophytes and non-dermatophytic moulds. In particular, HXP124 has excellent activity against dermatophytes that infect skin and nails.  In addition, HXP124 efficiently and rapidly penetrates human nails making it an ideal target for development of a novel onychomycosis treatment. Onychomycosis, or fungal infection of the nail, affects about 14% of the population. These infections are long-term, hard to treat, can be painful and have a cosmetic impact to the patient. Treatment options include systemic and topical therapies. Although effective, systemic therapies commonly have adverse effects, such as liver toxicity. Current topical have low cure rates due to poor nail penetration, and thus typically require long treatment times. The objectives of this study were to assess the activity of HXP124 against the major causative agents of onychomycosis and test its effectiveness in an Infected Nail Model. 


Methods: HXP124 was assessed in an Infected Nail Model whereby human toenail clippings were infected on the underside with Trichophyton rubrum and HXP124 was applied to the surface of the nail daily for 7, 14 or 21 days. Cell killing by HXP124 was also monitored using several methods including propidium iodide uptake, a PrestoBlue® assay and the ability of cells to grow on nutrient agar after treatment. HXP124 was assessed for toxicity in a 6-week GLP minipig dermal toxicity study.

Results: HXP124 effectively killed greater than 95% of T. rubrum cells within 7 days in an infected nail model. HXP124 also kills fungal cells more rapidly and at lower concentrations than current antimycotic drugs including efinaconazole and terbinafine. HXP124 did not induce dermal irritation in a minipig study at greater than 10-times the concentration intended for clinical use.

Conclusions: HXP124 is a potent antifungal molecule that efficiently penetrates human nails making it an excellent candidate for the development of a novel treatment for onychomycosis.

3 / The plant defensin HXP124 has the potential to be a new safe and effective topical treatment for onychomycosis