Developing new treatments for the blinding protozoan eye infection Acanthamoeba keratitis

Acanthamoeba is a free-living amoeba that can found in virtually all soil and water habitats throughout the world. Acanthamoeba lives in all of our homes and can be isolated from kitchen/bathroom taps, showerheads, vacuum cleaner dust and garden soil. The organism usually feeds bacteria but is an opportunistic pathogen of humans causing a fatal encephalitis in immunocompromised patients as well as a blinding infection of the eye called Acanthamoeba keratitis (AK).

AK is usually found in contact lens wearers and occurs through poor hygiene practices which include sleeping in lenses, storing lenses in tap water and not disinfecting lenses properly. In the UK there are approximately 5 million contact lens and approximately 200 cases of the infection each year. What is particularly worrying about this infection is that there is currently no licenced treatment. An unlicensed treatment does exist which includes the swimming pool disinfectant polyhexamethylene biguanide (PHMB). However, many patients particularly those diagnosed late do not respond to the treatment and suffer irreversible destruction of the corneal tissue requiring repeated corneal transplantation and eventually surgical removal of the eye.

Therefore there is an urgent need to identify new treatments and drug targets for this infection. Compounds including triazoles, biguanides, diamidines and amidoamines have previously demonstrated activity against Acanthamoeba. This proposal will involve the synthesis of novel compounds from the above classes to be tested against trophozoites and cysts of Acanthamoeba. Testing will utilise a high throughput screening assay and the best candidate compounds for further development will be identified by analysing the structure activity relationships (SAR) of the compounds