Drugging the schistosome zinc-dependent HDACs: current progress and future perspectives

Area of Science:

• Parasitology
• Epigenetics
• Drug Discovery

Background:

• Eukaryotic pathogens like schistosomes exhibit distinct life cycle stages regulated by epigenetic mechanisms.
• Targeting these epigenetics-driven cellular programs presents a vulnerability in parasitic organisms.
• Repurposing existing drugs for epigenetic therapies offers a faster route to novel antiparasitic agents.

Purpose of the Study:

• To review the development of drug leads targeting histone deacetylases (HDACs) in schistosomes.
• To highlight the potential of epigenetic enzyme inhibition as a therapeutic strategy against schistosomiasis.

Main Methods:

• Focus on zinc-dependent histone deacetylases (HDACs) as key epigenetic targets.
• Review progress in developing inhibitors for Schistosoma mansoni HDAC8 (smHDAC8).

Main Results:

• Development of drug leads inhibiting schistosome HDACs is advancing.
• Targeting smHDAC8 has shown proof of concept for treating schistosome infections.

Conclusions:

• Inhibiting epigenetic enzymes, particularly smHDAC8, is a validated approach for treating schistosomiasis.
• This strategy holds potential for developing antiparasitic therapeutics against other eukaryotic pathogens.