Funded Research Project Update: Use of pre-clinical EHE models to identify druggable pathways to treat EHE

Investigator: John Lamar, PhD, Albany Medical College

Dr. Lamar was awarded a 3-year grant by The EHE Foundation in 2022, that aims to identify FDA-approved drugs that inhibit EHE cell growth, and then test them in pre-clinical mouse models for the treatment of EHE.

What does this mean for patients? This could mean a shorter path to an FDA-approved treatment for EHE, since these drugs have been tested and proven safe for other diseases.

Dr. Lamar reports that they made significant progress in their first year of funding: 

Shortly after the project was funded the first EHE cell lines were established by Dr. Brian Rubin. In collaboration with Dr. Rubin, we have been working with these cell lines and have completed the extensive characterization and optimization necessary to effectively use these cells in assays required for this project. We have also demonstrated that inhibition of TAZ-CAMTA1-TEAD activity blocks the growth of these cells, indicating that targeting TAZ-CAMTA, TEADs, or other pathways that regulate them is a good therapeutic approach for EHE. 

In addition, we have established pre-clinical tumor models of EHE in mice using these cells. This was important as it will allow us to perform preclinical experiments mentioned above. With all optimizations nearly complete we are in the process of performing a small drug screen that has the potential to identify compounds that could block EHE cell growth, but also serves as a proof-of-concept experiment to demonstrate that our screening approach will work on a larger scale. 

The drug screen is ongoing, but preliminary results suggest we have identified some compounds that block EHE cell growth. These drugs will be evaluated further and if they remain promising, we will test them in our pre-clinical mouse models of EHE. In addition, these results show that our screening approach works well so we are preparing to do the larger RNAi screen that we proposed.

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