Therapeutic development ALS challenging

Therapeutic development for ALS has been challenging for many reasons, including the extreme variability in patient presentation, but also due to the many biological pathways that are affected and contribute to motor neuron degeneration.

The latter makes it exceedingly hard to choose and develop a drug for ALS that is expected to be efficacious on the basis of 1 biological target or biological pathway only. Combining compounds to engage multiple disease targets or pathways simultaneously is likely the best way forward. But unfortunately models to predict the effects of such combinations and the availability of multiple compounds simultaneously is not common.

Engage different targets and mechanisms

Most research groups or companies pursue 1 drug or 1 target in ALS at a time. Due to our collaboration with Raya Therapeutic, we have access to their 5 compounds to assess for combined efficacy in ALS motor neuron degeneration. These compounds all engage different targets and mechanisms of action that are known to contribute to motor neuron degeneration in ALS. Our access to these same compounds for an exploratory combinatorial assay design and analysis is a unique opportunity.

Goal project

In this project, will generate cell based assays to test the potential of combinations of compounds simultaneously. Induced pluripotent stem cell (IPSC) technology has allowed for the generation of cell lines from patient biosample donation, which are then differentiated into cell types that are usually not available for sampling from a patient, e.g. (motor) neurons. We will then use this system to test all 1 + 1 combinations of compounds from our collaborator.

Applicant project: Montreal Neurological Institute, Montreal, Quebec, Canada