Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads

Introduction: Naegleria fowleri is responsible for primary amebic meningoencephalitis (PAM) which has a fatality rate of >97%. Because of the rarity of the disease, pharmaceutical companies do not pursue new drug discovery for PAM. Yet, it is possible that the infection is underreported and finding a better drug would have an impact on people suffering from this deadly infection. Areas covered: This paper reports the efforts undertaken by different academic groups over the last 20 years to test different compounds against N. fowleri. The drug discovery research encompassed synthesis of new compounds, development and use of high-throughput screening methods and attempts to repurpose clinically developed or FDA-approved compounds for the treatment of PAM. Expert opinion: In absence of economic investment to develop new drugs for PAM, repurposing the FDA-approved drugs has been the best strategy so far to identify new leads against N. fowleri. Increasing use of high-throughput phenotypic screening has the potential to accelerate the identification of new leads, either in monotherapy or in combination treatment. Since phase II clinical trial is not possible for PAM, it is critical to demonstrate in vivo efficacy of a clinically safe compound to translate the discovery from lab to the clinic.