Open AccessThe PDE1/5 Inhibitor SCH-51866 Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington’s Disease
Author(s) -
Vahri Beaumont,
Larry Park,
Arash Rassoulpour,
Ulrike Dijkman,
Taneli Heikkinen,
Kimmo Lehtimäki,
Outi Kontkanen,
Rand Al Nackkash,
Gillian P. Bates,
Melanie Gleyzes,
Esther Steidl,
Sylvie Ramboz,
Carol A. Murphy,
Maria Beconi,
Celia Dominguez,
Ignacio Muñoz-Sanjuán
Publication year - 2014
Publication title -
plos currents
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.282
H-Index - 49
ISSN - 2157-3999
DOI - 10.1371/currents.hd.3304e87e460b4bb0dc519a29f4deccca
Subject(s) - pathogenesis , huntingtin , huntington's disease , disease , phosphodiesterase , polyglutamine tract , dosing , pharmacology , medicine , bioinformatics , biology , immunology , biochemistry , enzyme
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.