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Published on: October 11, 2013
Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads
1Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Abstract:
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.
Insights
Drug discovery for primary amebic meningoencephalitis (PAM) is limited due to its rarity. Repurposing FDA-approved drugs and high-throughput screening are key strategies to find new treatments for this deadly infection.
Area of Science:
- Neuroparasitology
- Drug Discovery
- Infectious Diseases
Background:
- Primary amebic meningoencephalitis (PAM) is caused by *Naegleria fowleri* and has a fatality rate exceeding 97%.
- Limited pharmaceutical investment in PAM drug discovery due to disease rarity.
- Potential underreporting of PAM cases necessitates improved treatment options.
Purpose of the Study:
- To review academic efforts in identifying new anti-*Naegleria fowleri* compounds over the past 20 years.
- To highlight strategies for drug discovery in the context of PAM.
Main Methods:
- Synthesis of novel chemical compounds.
- Development and application of high-throughput screening (HTS) methods.
- Repurposing existing clinically approved drugs for PAM treatment.
Main Results:
- Drug repurposing of FDA-approved medications has emerged as a primary strategy for identifying *N. fowleri* leads.
- HTS has shown potential to accelerate the discovery of novel monotherapies or combination treatments.
- Academic research has explored various compounds and screening approaches.
Conclusions:
- Drug repurposing is currently the most viable strategy for PAM drug discovery due to economic constraints.
- High-throughput phenotypic screening can expedite the identification of effective anti-*N. fowleri* agents.
- Demonstrating *in vivo* efficacy of safe compounds is crucial for clinical translation, especially given the challenges of PAM clinical trials.
