title: The PDE1/5 Inhibitor SCH-51866 Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington's Disease.
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.
authors.affiliation: CHDI Management/CHDI Foundation, Los Angeles, California, USA.
authors.forename: Vahri
authors.initials: V
authors.lastname: Beaumont
authors.affiliation: CHDI Management/CHDI Foundation, Los Angeles, California, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Park
authors.affiliation: Brains On-Line LLC, South San Francisco, California, USA.
authors.forename: Arash
authors.initials: A
authors.lastname: Rassoulpour
authors.affiliation: Brains On-Line LLC, South San Francisco, California, USA.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dijkman
authors.affiliation: Charles River Discovery Research Services, Kuopio, Finland.
authors.forename: Taneli
authors.initials: T
authors.lastname: Heikkinen
authors.affiliation: Charles River Discovery Research Services, Kuopio, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Lehtimaki
authors.affiliation: Charles River Discovery Research Services, Kuopio, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Kontkanen
authors.affiliation: Department of Medical and Molecular Genetics, Kings College London, London, UK.
authors.forename: Rand
authors.initials: R
authors.lastname: Al Nackkash
authors.affiliation: Department of Medical and Molecular Genetics, Kings College London, London, UK.
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Bates
authors.affiliation: Neuroservice, Domaine de Saint Hilaire, 13593 Aix en Provence cedex 03, France.
authors.forename: Melanie
authors.initials: M
authors.lastname: Gleyzes
authors.affiliation: Neuroservice, Domaine de Saint Hilaire, 13593 Aix en Provence cedex 03, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Steidl
authors.affiliation: PsychoGenics Inc., Tarrytown, New York, USA.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ramboz
authors.affiliation: PsychoGenics Inc., Tarrytown, New York, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Murphy
authors.affiliation: CHDI Management/CHDI Foundation, Los Angeles, California, USA.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Beconi
authors.affiliation: CHDI Management/CHDI Foundation, Los Angeles, California, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: Dominguez
authors.affiliation: CHDI Management/CHDI Foundation, Los Angeles, California, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Munoz-Sanjuan