New ALS Drug Screening Platform Identified; Leads to Early-Stage Drugs of Promise

Q&A with Project ALS Researcher Dr. Sebastian Thams, Karolinska Institute, on His Recent Discovery, Published in Molecular Therapy

Can you describe your discovery that was recently published in Molecular Therapy?

In our recent paper, we present a new screening platform, in which we elicit neurodegeneration by exposing ALS motor neurons to a biological stressor. We used this assay to screen for neuroprotective compounds reversing ALS-associated cell stress. We identified two groups of promising compounds, which increased motor neuron survival in mouse and human cultures, and delayed loss of muscle nerve endings in ALS mice. These compounds included protein kinase inhibitors and a bile acid. Altogether, our results have now enabled us to start the development of completely new drugs for ALS.

How does this discovery add to the field of ALS drug testing?

Our study demonstrates that stem cell-based screening models are valuable tools for swift and robust evaluation of potential drug candidates. As a proof-of-concept, we showed neuroprotective drug effects in mouse and human cell cultures, as well as in muscles from ALS mice, thereby strengthening the notion that important results from cells in cultures can be applied to ALS patients in the future.

How does this bring us closer to treatments for patients? 

We have now identified promising compounds that reverse disease-related processes in motor neurons. While most of these compounds are not suitable for direct testing in patients in their present form, they possess important neuroprotective properties, which we are now taking advantage of. The compounds are in the process of refinement and modification to be more suitable for treatment in patients. We are optimistic that the compounds can soon be ready for testing in ALS patients.

How has Project ALS affected your career?

Project ALS has created a stimulating academic environment for cutting edge translational stem cell research, which I had the great opportunity to be a part of during my time at Columbia University. My experience at the Project ALS laboratory provided me with essential tools that I now use in my own laboratory. The nurturing setting fostered an invaluable international network, which I benefit from in current collaborations.

What did you focus on in your early work with Project ALS? 

I was particularly interested in setting up new platforms for drug screening using stem cell-derived neurons. I focused specifically on the intrinsic properties of motor neurons that render them susceptible to neurodegeneration. My outstanding goal was to gain new insights into motor neuron vulnerability, and subsequently, use this knowledge to design new therapies for ALS.

What else have you been working on recently? 

I presently divide my time between working as a physician and a scientist at the Department of Neurology, Karolinska University Hospital in Stockholm, Sweden. I am involved in both clinical trials for new ALS treatments and basic research projects related to cell stress mechanisms in ALS. Time management is a struggle when you split your attention, but I have the great opportunity to work on projects ranging from cells to patients. My goal is to improve the clinical management for ALS patients, and hopefully contribute to the development of more potent treatments for the disease.

Read the published study here.