The PDE1/5 Inhibitor SCH-51866 Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington's Disease

PLoS Curr. 2014 Feb 13;6:ecurrents.hd.3304e87e460b4bb0dc519a29f4deccca. doi: 10.1371/currents.hd.3304e87e460b4bb0dc519a29f4deccca.

Abstract

Huntington's disease is a neurodegenerative disorder caused by mutations in the CAG tract of huntingtin. Several studies in HD cellular and rodent systems have identified disturbances in cyclic nucleotide signaling, which might be relevant to pathogenesis and therapeutic intervention. To investigate whether selective phosphodiesterase (PDE) inhibitors can improve some aspects of disease pathogenesis in HD models, we have systematically evaluated the effects of a variety of cAMP and cGMP selective PDE inhibitors in various HD models. Here we present the lack of effect in a variety of endpoints of the PDE subtype selective inhibitor SCH-51866, a PDE1/5 inhibitor, in the R6/2 mouse model of HD, after chronic oral dosing.

Grant support

All studies are conducted by CROs or academic labs (Bates laboratory) and are funded solely using funds provided by CHDI Foundation for the work described in this paper.