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 defensins makes them extremely stable and able to withstand extremes of pH and temperature. Here we report for the first time on the pre-clinical and clinical testing of the plant defensin HXP124 as a treatment for fungal nail infections in humans.
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. Onychomycosis, or fungal infection of the nail, affects about 10-12% of the population. These infections are long-term, hard to treat, can be painful and have a cosmetic impact on the patient. Treatment options encompass both systemic and topical therapies. Systemic therapies are effective but commonly have adverse side effects, such as liver toxicity. Current topical treatments have low cure rates largely due to poor nail penetration, and typically require long treatment times.
HXP124 is highly selective for fungi and kills fungal cells within 30 min of exposure. Surprisingly, HXP124 rapidly and efficiently penetrates human nails allowing it to accumulate at the site of infection in the nail bed within 24 h. HXP124 has an excellent safety profile in pre-clinical toxicology studies, including a repeat-dose minipig dermal irritation study.
HXP124 was tested for safety, tolerability and efficacy in a double-blind, vehicle-controlled, phase1/2a first-in-human clinical study. HXP124 was safe when applied topically. There were no treatment‐related adverse events during the study and HXP124 did not cause pain or irritation in the treated toes. HXP124 was not detected in the bloodstream and it substantially reduced the area of diseased nail in patients relative to the vehicle-treated control in the 12 week study period.
Combined, these attributes make HXP124 an excellent candidate for a fast, effective topical treatment for onychomycosis.