WPs » WP10

WP10

Workpackage 10: Valorization

Nr

Objective

1

To validate the proof of concept on targeting 3 to 5 proteins found by systems biology models affecting ALS

2

To find new therapeutic agents for ALS: we expect to end up with 1 to 3 preclinical leads

3

To obtain IP on leads found in this WP: expected one issued patent

4

To acquire chemical/biological knowledge for dissemination in WP1

 

We envision that the valorization process will be an intensive interplay between partners of the Euro-MOTOR consortium and an SME. It will be initiated by screening human motor neurons derived from IPs and other neuronal cellines (e.g. NSC34), genetically modified in line with discovered targets/pathways as being causal to ALS (identified in WP 9 in collaboration with all other WPs) during the project at the high throughput screening cellulomics facility at the UMC Utrecht using compound libraries available at the UMC Utrecht (natural products, generic (off label, off patent) products) or those obtained from Pharma or Biotech companies. In addition, we can perform small molecule- and siRNA screens aimed at identifying molecular pathways or compounds that positively influence ALS pathology: a library of over 50.000 small molecule compounds, of which approximately 5000 with known biological activity, as well as a comprehensive shRNA knockdown library that allows the knockdown of specific molecular pathways are available at the UMC Utrecht cellulomics facility. From that an SME will be involved to identify the most drugable compound by defining its chemical structure, producing analogues of the compounds, determining the structure activity relationship (SAR), its potential to cross the blood-brain barrier, solubility and pharmacokinetics. Subsequently, partners of the Euro-MOTOR consortium could play a role in validating the effect of promising compounds in animal models.

We expect to present a definite workplan for WP10 from 24 months after onset of Euro-MOTOR.