BRAVEinMS rises from the joint efforts of laboratories from five different countries in Europe and North America with the aim of merging and synergizing unique competences in order to identifying promising molecules that can counteract the progression of multiple sclerosis (MS). The project aims at detecting potential therapeutic compounds to be rapidly translated into the clinic with a fast-forward step-wise process that can also, indirectly, unveil mechanisms controlling progressive neuronal damage or impaired myelin regeneration.
A robust virtual network pharmacological screening on large libraries of registered and safe-in-human molecules will be implemented and hits with suggestive therapeutic potential will be tested in cell-based in-vitro pharmacological experiments. Rodent as well as human neuro-glia cells will be used as first line screening platform with particular attention to robustly reproduce the data in the human cellular context and in several laboratories to reduce the number of false-negative hits. As a second line screening system, induced pluripotent stem cell (iPSC)-derived neural progenitors from MS patients will be used in order to have a disease-in-a-dish tool for human validation studies essential for assessing the disease specificity of our results. Finally, compounds found efficacious in vitro will be extensively evaluated in vivo in several animal models each one representing a clinico-pathological key aspect of the neurodegenerative process occurring in MS patients.
The process will leverage the unique expertise from each participating group. Careful in vitro screening represents a main critical pillar in the project and is designed to identify molecules with promising therapeutic potential whose efficacy will be ultimately tested in innovative neurodegenerative and demyelinating preclinical disease models. Within the goal of this Progressive MS Alliance call, BRAVEinMS should pinpoint a limited number of previously unidentified molecules with high chance of therapeutic power in progressive MS patients, pharmacokinetic flexibility and minimal side effects.
Compared to conventional drug-discovery pipeline or to previous published work achieved with rodent cells, the approach proposed by BRAVEinMS focusing on modular and well controlled bioinformatics tools followed by stringent biological filtering criteria as well as on human neural cells from MS patients will result in a higher chance of robustness and disease specific relevance. Owing to that, we aim at implementing a MS clinical trial by end of 2020