Development of novel antimicrobial therapy for Acanthamoeba Keratitis

Brief background

Acanthamoeba keratitis (AK) is a serious cause of infectious keratitis in both developed and developing countries. Although relatively uncommon, a recent study has shown a rising incidence of AK to one in 21000 among contact lens wearers. In addition, it is an extremely painful disease that often results in poor clinical outcome, with ~40% requiring surgical interventions. This is primarily attributed to the delay in diagnosis, limited treatment options, resistance to treatment, and potential side-effects related to the anti-acanthamoebic treatment (AAT).

Successful treatment of AK requires eradication of trophozoites (active form) and cysts (dormant form).

However, the latter are impervious to most antibiotics and contact lens solution, posing significant therapeutic challenges.

However, despite intensive treatment, poor visual outcome and complications such as corneal perforation and loss of sight may still ensue. All these issues highlight an unmet need for alternative treatment for AK.

What problem/knowledge gap does it help address

Host defense peptides (HDPs), also known as antimicrobial peptides, are evolutionarily conserved molecules that play vital roles in the immune system.

HDPs have recently shown promise as potential therapeutic agents, due to their broad-spectrum antimicrobial properties with minimal risk of developing antimicrobial resistance, against a wide array of infections, including drug-resistant bacteria, fungi, Acanthamoeba, and viruses. These molecules are therefore a good option to investigate as an alternative treatment for AK.

Aim of the research project

To develop novel HDPs with enhanced efficacy and safety to treat AK.

Key procedures/objectives

1. Examine the in vitro anti-acanthamoebic efficacy of HDPs.
2. Further optimise and refine the HDPs to improve anti-acanthamoebic efficacy.
3. Examine the potential synergism or additive action between treatment methods.

Potential impact on people with sight loss

AK can cause serious corneal infection, for which the current treatment is very limited. Successful development of a novel therapy can potentially improve the visual outcome and improve the quality of life of the affected patients.