The Susceptibility of Trypanosomatid Pathogens to PI3/mTOR Kinase Inhibitors Affords a New Opportunity for Drug Repurposing
2011

New Drug Opportunities for Treating Trypanosomatid Infections

Sample size: 5 publication 10 minutes Evidence: moderate

Author Information

Author(s): Diaz-Gonzalez Rosario, Kuhlmann F. Matthew, Galan-Rodriguez Cristina, da Silva Luciana Madeira, Saldivia Manuel, Karver Caitlin E., Rodriguez Ana, Beverley Stephen M., Navarro Miguel, Pollastri Michael P.

Primary Institution: Instituto de Parasitología y Biomedicina “López-Neyra” Consejo Superior de Investigaciones Cientificas, Granada, Spain

Hypothesis

Can inhibitors targeting the PI3K/mTOR pathway be effective against trypanosomatid parasites?

Conclusion

The study suggests that PI3K/mTOR inhibitors, particularly NVP-BEZ235, show promise as potential treatments for African sleeping sickness.

Supporting Evidence

  • NVP-BEZ235 showed sub-nanomolar potency against cultured parasites.
  • The study identified 12 proteins in trypanosomatids that are potential drug targets.
  • NVP-BEZ235 significantly extended survival in mice infected with T. brucei.
  • Other inhibitors showed micromolar efficacy against the parasites.
  • The approach of target repurposing was validated as an effective strategy.

Takeaway

Scientists tested some drugs to see if they could help fight diseases caused by tiny parasites. One drug, NVP-BEZ235, worked really well and could help treat sick people.

Methodology

The study tested 8 inhibitors against various trypanosomatid parasites in vitro and in vivo.

Potential Biases

Potential bias in selecting only certain inhibitors for testing.

Limitations

The study primarily focused on a limited number of compounds and did not explore all potential inhibitors.

Participant Demographics

Mice were used in the in vivo studies, specifically Balb/C mice.

Statistical Information

P-Value

0.73

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pntd.0001297

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