The new research focuses on one such aberrant protein, TDP-43, which binds to RNA in the cell’s nucleus and is responsible for regulating thousands of human genes. If TDP-43 turns from a healthy, liquid-like phase into diseased, fibrous solid-like aggregates, its presence can be fatal.

This protein is one of the key drivers of the diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)—a discovery first made by pioneering Penn Medicine scientists Virginia M.-Y. Lee, Ph.D., MBA, and the late John Trojanowski, MD, Ph.D.

There are currently no cures for ALS or FTD, but that could change. In a study published in Science, researchers at the Perelman School of Medicine at the University of Pennsylvania reported short RNA molecules that could reverse TDP-43 aggregation and restore its function, an important advance toward RNA-based treatments for ALS and FTD.