Therapeutic targets and investigated treatment strategies in Acanthamoeba keratitis

ABSTRACT

Introduction: Free Living Amoebae (FLA) are unicellular protozoa common to most soil and aquatic environments. Only members of the genus Acanthamoeba and the species Naegleria fowleri, Balamuthia mandrillaris and Sappinia diploidea are known to infect humans and other animals, often with fatal consequences. Acanthamoeba species are the causative agents of a sight threating infection of the cornea known as Acanthamoeba keratitis (AK) that mainly affects immunocompetent contact lens wearers and has shown an increased incidence in the recent years worldwide. To date, most of the available treatments and contact lens maintenance solutions are not fully effective against these pathogens.

Areas covered: There is a clear need for novel fully effective therapeutic agents against AK. In the recent years the application of ‘phylopharmacology’ and RNAi has shown to be a reliable tool for the elucidation of novel drug targets and therapeutic agents. Current therapeutic options for AK as well as ongoing research advances are presented and discussed.

Expert opinion: The available AK treatments are not fully effective so far mostly due to the existence of a cyst stage in this pathogen. Moreover, most of the first line treatment options are not available in all countries. There is an urgent need to validate novel drug targets and therapeutic agents against AK. Recent approaches have allowed the validation of drug targets and novel compounds that could become fully effective therapies against these emerging pathogens.

KEYWORDS:

• Acanthamoeba
• contact lenses
• keratitis
• cyst
• therapy
• RNAi

Article highlights

• Acanthamoeba keratitis is a sight-threating infection of the cornea which is increasing worldwide mainly among contact lens wearers.

• Current first line treatments include biguanides (Chlorhexidine and PHMB) and a diamidine, involving a lengthy and toxic therapeutic approach.

• Research focused on the discovery of novel therapeutic approaches have reported so far good alternatives for AK treatment such as statins, miltefosine and new formulations of PHMB.

• Further research is in urgent need in order to establish a fully effective therapy against AK.

This box summarizes key points contained in the article.

Acknowledgments

This review is dedicated to the Acanthamoeba keratitis facebook support group.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by the grants RICET (project no. RD12/0018/0012 of the programme of Redes Temáticas de Investigación Cooperativa, FIS), Spanish Ministry of Health, Madrid, Spain, the Project PI13/00490 ‘Protozoosis Emergentes por Amebas de Vida Libre: Aislamiento, Caracterización, Nuevas Aproximaciones Terapéuticas y Traslación Clínica de los Resultados’ from the Instituto de Salud Carlos III, and Project ref. AGUA3 ‘Amebas de Vida Libre como Marcadores de Calidad del Agua’ from CajaCanarias Fundación. J Lorenzo-Morales was supported by the Ramón y Cajal Subprogramme from the Spanish Ministry of Economy and Competitivity RYC-2011-08863.