Ex Vivo Insect BBB Model

N2MO has patented an invertebrate ex vivo system, based on a natural biological brain barrier from the locust grasshopper (Locusta Migratoria or Schistocerca Gregaria), that can be used to screen and rank compounds to identify drug leads with improved BBB properties.

The model can replace standard in vitro screen models with an additional opportunity for identification of P-glycoprotein (Pgp) substrates in the early screen cascade. All this whilst meeting the drug discovery demands for reliability, time and cost efficiency.

In the ex vivo Locust BBB model compound permeability is studied at constant brain exposure of  1-10 µM and is independent of degrading enzymes, elimination and plasma protein binding. The model opens possibility for testing dose/time response over an intact barrier system. Data quality is high and the study outcome is always judged towards the response of an internal positive control.

Key Model Advantages

  • The locust blood brain barrier is a natural biological brain barrier that retains its biological integrity and control functions during the test procedure similar to vertebrate in
 vivo BBB models.
  • The ex vivo Locust BBB permeability model is the only existing ex vivo model of BBB
 permeability that is based on an intact bio-membrane.
  • The Locust brain barrier contains a Pgp efflux mechanism that can be inhibited 
by verapamil and the ex vivo BBB locust permeability model is a valuable tool for the
 identification of Pgp substrates and inhibitors. The Pgp inhibitor, verapamil, can be included in the test protocol for identification of active Pgp mediated transport.
  • Only a small amount of compound material is needed for the ex vivo BBB permeability model and re-synthesis of compound is rarely necessary.
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