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Repurposing of Nitroxoline as an Alternative Primary Amoebic Meningoencephalitis Treatment

Javier Chao-Pellicer1,2,3, Iñigo Arberas-Jiménez1,2, Frieder Fuchs4,5

  • 1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Spain.

Antibiotics (Basel, Switzerland)
|August 26, 2023
PubMed

Insights

Nitroxoline shows potent activity against Naegleria fowleri, the cause of primary amoebic meningoencephalitis (PAM). This drug repurposing offers a promising new treatment strategy for this fatal parasitic infection.

Area of Science:

  • Infectious Diseases
  • Parasitology
  • Drug Discovery

Background:

  • Pathogenic free-living amoebae (FLA), including Naegleria fowleri, cause severe central nervous system infections.
  • Primary amoebic meningoencephalitis (PAM) is a rapidly fatal disease with a high mortality rate (>97%).
  • Current treatment options for PAM are limited and often ineffective, necessitating the search for novel therapeutic agents.

Purpose of the Study:

  • To evaluate the anti-parasitic activity of Nitroxoline against Naegleria fowleri.
  • To assess Nitroxoline's efficacy against both trophozoite and cyst stages of N. fowleri.
  • To determine the therapeutic potential of Nitroxoline as a repurposed drug for PAM treatment.

Main Methods:

  • Drug repurposing approach testing Nitroxoline's efficacy.
  • In vitro assays to determine IC50 values against N. fowleri trophozoites and cysts.
  • Assessment of Nitroxoline's activity in comparison to its toxicity in host cells.

Main Results:

  • Nitroxoline demonstrated low micromolar activity against N. fowleri trophozoites (IC50 values of 1.63 ± 0.37 µM and 1.17 ± 0.21 µM).
  • Effective activity was also observed against N. fowleri cyst stages (IC50 of 1.26 ± 0.42 μM).
  • Nitroxoline exhibited favorable selectivity indices (3.78 and 5.25) in previous studies on host cells, indicating a good safety profile.

Conclusions:

  • Nitroxoline possesses potent anti-parasitic activity against Naegleria fowleri.
  • The drug induces programmed cell death (PCD)-related events in N. fowleri.
  • Nitroxoline is a promising candidate for the development of an alternative treatment for primary amoebic meningoencephalitis.
Keywords:
8-hydroxy-quinolineNaegleria fowleriNitroxolinedrug repurposingprimary amoebic meningoencephalitisprogrammed cell death

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