AFTD has partnered with the Alzheimer’s Drug Discovery Foundation (ADDF) since 2007 to support preclinical research on promising new drugs through the Accelerating Drug Discovery for FTD program. We are proud to announce Jeffrey Rothstein, MD, PhD, a professor of neurology and director of the Robert Packard Center for ALS Research at Johns Hopkins University, as the most recent recipient of an Accelerating Drug Discovery for FTD award.

Dr. Rothstein’s project, Mitigating TDP-43 loss of function and disease initiation in FTD through repair of the nuclear pore and CHMP7/ESCRT3 dysfunction, will evaluate a novel therapeutic to correct a problem at the heart of FTD associated with the accumulation of the protein TDP-43 – the abnormal relocation of TDP-43 from the nucleus of brain cells to the surrounding cell matrix. Previous work by Dr. Rothstein and others have implicated injury to a structure called the nuclear pore as a key factor in TDP-43’s migration.

In this project, he and his team will examine a type of drug known as an antisense oligonucleotide (ASO) intended to correct the injury to the nuclear pore. Using cells derived from persons carrying a harmful variant of the C9orf72 gene, they will confirm the beneficial effect of the ASO on the nuclear pore, determine whether this restores the normal location and function of TDP-43, and check for any unexpected or negative effects on the cells. If the ASO passes these tests, Dr. Rothstein will then carry out further testing in mice to lay the groundwork for a future clinical trial.