Neurology

Mouse studies suggest inhibiting the FOSB/HDAC1 axis could help treat AD. In dentate gyrus tissue samples from a mouse model of AD, levels of a truncated FOSB isoform were higher and levels of c-Fos, which is down-regulated by FOSB isoform-dependent HDAC1 activity, were lower than in dentate gyrus samples from normal mice. Also in the model, injection into the dentate gyrus of an adeno-associated viral (AAV) vector encoding a truncated version of AP-1 that inhibited the FOSB isoform's activity, subcutaneous injection of the HDAC inhibitor entinostat, or intraperitoneal (i.p.) injection of the generic HDAC inhibitor 4-phenylbutyric acid increased spatial memory compared with empty vector or vehicle. Next steps could include identifying and testing small molecule inhibitors of the FOSB isoform in models of AD.

4-phenylbutyric acid is marketed to treat urea cycle disorder...