Workpackage 3: Targeting combinatorial disease-modifying treatments into the brain
Objectives of the Workpackage
It will be of paramount importance to have the ability to target combinatorial treatments to the brain. This workpackage will develop versatile tools to serve this goal. Specific objectives are the following:
- Developing liposomal encapsulation for improving drug delivery across the BBB: Molecules of interest for potential treatment of epileptogenesis and epilepsy identified by the research institutes in WP2 will be encapsulated in liposomes. These methods will provide small volumes of molecules in these brain-targeted liposomes that can be used by the research institutes to start experiments in models of epilepsy and epileptogenesis.
- Developing liposomal encapsulation for combinatorial biologics delivery across the BBB: This task will deliver techniques for the encapsulation of larger, more complex molecules. Also, it will study if combinations of these liposomes, or even combinations of molecules within a liposome, will further benefit potential treatment.
- Developing amplicon vectors for long-term gene expression into the brain: Major limitations for the development of a gene therapy approach are the safety, the specificity and the sustained production of biological compounds in a localized area of an organism. This task will develop techniques for safe and efficient gene expression systems perfectly suited for specific regions of the brain (e.g.: hippocampus).
- Developing multigenic amplicon vectors for efficient combinatorial gene delivery: As epilepsy very likely arises from a multifactorial brain disorder (epileptogenesis), a combinatorial gene therapy approach will surely be more efficient in inhibiting epileptic seizures. This task will therefore create vectors allowing the simultaneous expression of many genes and microRNA. These combinatorial tools will be evaluated by members of EPITARGET in various epileptic animal models.
- Rational drug discovery/development program. During the project, several potential treatments will be developed with the intention to have data on disease effect and production ready at end of project.