There are no effective treatments frontotemporal dementia (FTD), a debilitating disease where specific nerve cells die in specific parts of the brain. A unifying feature of ~9% of FTD cases is the aberrant clumping of a protein called FUS in the nerve cells that die. Approaches that reverse the aberrant clumping of FUS and restore its normal behavior are anticipated to be an effective therapeutic strategy. We have designed short nucleic acid drugs that reverse aberrant FUS clumping and restore normal FUS behavior. In the proposed work, we plan to optimize these drugs and assess their efficacy in patient cells and mouse models of FTD with the goal of advancing this approach toward the clinic for FTD patients.