Project: Glutamate Oxaloacetate Transaminase Nanoparticles targeted to the Brain for Neuroprotection in Ischemic Stroke
| Acronym | GOTTARG (Reference Number: EURONANOMED2019-116) |
| Duration | 01/01/2020 - 31/12/2022 |
| Project Topic | This project will develop and test the first targeted and long-acting nanomedicine with neuroprotective properties for ischemic stroke, and with potential application in other neurological diseases. The Team will demonstrate that the targeted delivery of a long-acting glutamate oxaloacetate transaminase (GOT) nanoparticle to- or near to- the brain enhances the neuroprotective character of GOT (i.e., prevention od neuronal apoptosis and cell death) in a model ischemic stroke, relative to GOT itself. Systemically-administered GOT has been demonstrated to deplete blood glutamate levels, which in turn causes an efflux of excess glutamate from the brain. However, one major shortcoming of this approach is that the systemic effect of GOT on brain glutamate concentration is short-lived (~1 h), mainly because of its rapid distribution and elimination from the body. Building upon the collective expertise of the Team, this project will i) increase the therapeutic half-life of GOT and ii) target GOT to- or near to- the ischemic region of the brain where GOT can exert its therapeutic catalytic activity. These objectives will be met by preparing a Blood-Brain-Barrier (BBB)-targeted nano-formulation of GOT (GOT-NP). What is particularly original in this strategy is that accumulation of GOT-NP at the blood-side of the BBB will promote the efflux of glutamate from the brain by increasing the glutamate gradient on either side of the BBB. As such, GOT-NP does not actually have to cross the BBB to produce an enhanced neuroprotective effect. Crossing the BBB, which is substantially more challenging, would represent an added bonus of selectively depleting glutamate in the cerebrospinal fluid. In addition to the design and synthesis of GOT-NP, this project will investigate iii) the mechanism of in vitro neuroprotection as well as iv) the in vivo biodistribution and neuroprotective effect of GOT-NP in an animal model of ischemic stroke. |
| Network | EuroNanoMed III |
| Call | Joint Transnational Call (2019) |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Institut National de la Recherche Scientifique (INRS) | Coordinator | Canada |
| 2 | Health Research Instituteof Santiago de Compostela (IDIS)-(former Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS)) | Partner | Spain |
| 3 | Sabanci University Nanotechnology Research and Application Center (SUNUM) | Partner | Türkiye |
| 4 | Norwegian Institute for Air research | Partner | Norway |