As part of our Center’s annual pilot project program, Dr. Sami Barmada and his team identified a potential therapeutic target for neurodegenerative conditions, including ALS and Frontotemporal dementia.
ALS and Frontotemporal dementia (FTD) are similar in both pathology and genetics, and researchers have long known that most people with ALS and FTD accumulate deposits of the protein TDP-43 in nerve cells. This build up is potentially responsible for the death of nerve cells in these two diseases. Dr. Barmada and his team’s most recent preclinical findings, published in Cell Reports, pinpoint a structure within the TDP-43 protein that is critical for the function of this protein and its ability to cause nerve cell death. In the process, they uncovered a potential clue to halt the destruction of nerve cells.
“By manipulating the structure of the protein,” Barmada says, “we determined that RNA binding is pivotal for maintaining the stability, function and toxicity of TDP-43 in disease models.”
The findings show that modifying TDP-43 structure eliminates its ability to bind RNA and cause nerve cell death in models of ALS and FTD. Targeting this structure opens the potential to explore new therapies for ALS and FTD.