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

Vahri Beaumont; Larry Park; Arash Rassoulpour; Ulrike Dijkman; Taneli Heikkinen; Kimmo Lehtimaki; Outi Kontkanen; Rand Al Nackkash; Gillian P. Bates; Melanie Gleyzes; Esther Steidl; Sylvie Ramboz; Carol Murphy; Maria G. Beconi; Celia Dominguez; Ignacio Munoz-Sanjuan

doi:10.1371/currents.hd.3304e87e460b4bb0dc519a29f4deccca

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

Vahri Beaumont, Larry Park, Arash Rassoulpour, Ulrike Dijkman, Taneli Heikkinen, Kimmo Lehtimaki, Outi Kontkanen, Rand Al Nackkash, Gillian P. Bates, Melanie Gleyzes, Esther Steidl, Sylvie Ramboz, Carol Murphy, Maria G. Beconi, Celia Dominguez, Ignacio Munoz-Sanjuan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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.

Original language	English
Article number	ecurrents.hd.3304e87e460b4bb0dc519a29f4deccca
Journal	PLOS Currents: Disasters
Issue number	FEB
DOIs	https://doi.org/10.1371/currents.hd.3304e87e460b4bb0dc519a29f4deccca
Publication status	Published - 2014

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10.1371/currents.hd.3304e87e460b4bb0dc519a29f4decccaLicence: CC BY

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Beaumont, V., Park, L., Rassoulpour, A., Dijkman, U., Heikkinen, T., Lehtimaki, K., Kontkanen, O., Al Nackkash, R., Bates, G. P., Gleyzes, M., Steidl, E., Ramboz, S., Murphy, C., Beconi, M. G., Dominguez, C., & Munoz-Sanjuan, I. (2014). The PDE1/5 Inhibitor SCH-51866 Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington's Disease. PLOS Currents: Disasters, (FEB), Article ecurrents.hd.3304e87e460b4bb0dc519a29f4deccca. https://doi.org/10.1371/currents.hd.3304e87e460b4bb0dc519a29f4deccca

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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.",

author = "Vahri Beaumont and Larry Park and Arash Rassoulpour and Ulrike Dijkman and Taneli Heikkinen and Kimmo Lehtimaki and Outi Kontkanen and {Al Nackkash}, Rand and Bates, {Gillian P.} and Melanie Gleyzes and Esther Steidl and Sylvie Ramboz and Carol Murphy and Beconi, {Maria G.} and Celia Dominguez and Ignacio Munoz-Sanjuan",

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Beaumont, V, Park, L, Rassoulpour, A, Dijkman, U, Heikkinen, T, Lehtimaki, K, Kontkanen, O, Al Nackkash, R , Bates, GP, Gleyzes, M, Steidl, E, Ramboz, S, Murphy, C, Beconi, MG, Dominguez, C & Munoz-Sanjuan, I 2014, 'The PDE1/5 Inhibitor SCH-51866 Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington's Disease', PLOS Currents: Disasters, no. FEB, ecurrents.hd.3304e87e460b4bb0dc519a29f4deccca. https://doi.org/10.1371/currents.hd.3304e87e460b4bb0dc519a29f4deccca

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AU - Rassoulpour, Arash

AU - Dijkman, Ulrike

AU - Heikkinen, Taneli

AU - Lehtimaki, Kimmo

AU - Kontkanen, Outi

AU - Al Nackkash, Rand

AU - Bates, Gillian P.

AU - Gleyzes, Melanie

AU - Steidl, Esther

AU - Ramboz, Sylvie

AU - Murphy, Carol

AU - Beconi, Maria G.

AU - Dominguez, Celia

AU - Munoz-Sanjuan, Ignacio

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AB - 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.

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

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