HD Unmet Clinical Research Needs: Perspective From the Pre-Manifest HD Population

Moser, Katharine; Aylward, Elizabeth H.; Stout, Julie C.; Queller, Sarah; Duff, Kevin; Tomusk, A.; Lifer, S.; Hastings, Somerville; Dawson, Jesse; Walker, Brittany; Pacifici, Robert E.; Hersch, Steven M.; Dorsey, E. Ray; Katz, Russell; Tempkin, Teresa; Wheelock, Vicki; Schwartz, G.; Corey–Bloom, Jody; Mattis, Paul J.; Feigin, Andrew; Young, P.; McArthur, David L.; Perlman, Susan; Higginson, Christopher I.; Carr, Laurence A.; Sigvardt, Karen A.; Chirieac, Madalina C; Shinaman, Aileen; Shoulson, Ira; Kane, Amy; Lessig, Stephanie; Wasserman, Linda; Tang, Chengke; Zgaljardic, Dennis J.; Ma, Yixuan; Dhawan, Vijay; Guttman, Mark; Eidelberg, David; Peng, Schichun; Kingsley, Peter B.; Rosas, H. Diana; Gevorkian, Sona; Oakes, David; Matson, Wayne R.; Massood, Tiffany; Latourelle, Jeanne C.; Mysore, Jayalakshmi Srinidhi; Fossale, Elisa; Gillis, Timothy E.; Gusella, James F.; MacDonald, Marcy E.; Myers, Richard H.; Yastrubetskaya, Olga; Preston, J. Samuel; Chiu, Edmond; Goh, Anita M Y; Oster, Emily; Bausch, Jan; Kayson, Elise; Quaid, Kimberly A.; Sims, Sharon L.; Swenson, Melinda M.; Harrison, Joan M.; Moskowitz, Carol; Stepanov, N.; Suter, Greg; Westphal, Bernd; Johnson, Shannon A.; Langbehn, Douglas R.; Paulsen, Jane S.; Nopoulos, Peg; Beglinger, Leigh J.; Johnson, Hans J.; Magnotta, Vincent; Pierson, Ronald; Lipe, Hillary; Bird, Thomas D.; McCusker, Elizabeth; Lownie, A.; Lechich, Anthony J.; Montas, Sacha; Duckett, Ayana; Klager, J.; Sandler, Simon J. I.; Pae, Ae Nim; Apostol, Barbara L.; Simmons, Danielle A.; Zuccato, Chiara; Illés, K.; Pallos, Judit; Casale, Malcolm; Kathuria, S. P.; Cattaneo, Elena; Marsh, J. Lawrence; Thompson, Leslie M.; Patzke, Holger; Chesworth, Richard; Li, Z.; RAHIL, G; Wang, J.; Smith, Jessica; Huet, F.; Shapiro, Gideon; LEIT, S; Beaulieu, Pierre; Raeppel, F.; Fournel, Mélanie; Sainte-Croix, H.; Nolan, Sarah J; Albayya, F. P.; Barbier, Annalisa; Besterman, J.; Ahlijanian, Michael K.; Deziel, R.; Aubeeluck, Aimée; Buchanan, Heather; Ross, Christopher A.; Biglan, Kevin; Landwehrmeyer, Bernhard; Whitlock, Kathryn B.; Carlozzi, Noelle E.; Mickes, Laura; Lee, J.; Kim, R. Y.; Toro, B. Di; Fine, Eric M.; Cahill, Timothy C.; Johnson, Douglas C.; Goldstein, Jody; Peavy, Guerry M.; Jacobson, Mark W.; Goodman, LaVonne; Como, Peter; Cha, J. H.; Beck, Christopher A.; Adams, Marie C.; Chadwick, G. A.; Blieck, Elisabeth A. de; McCallum, Colleen; Deuel, Lisa M.; Clarke, Angus; Stewart, R. Malcolm; Adams, W. H.; Paulson, Henry L.; Fiedorowicz, Jess G.; Hanson, J. M.; Ramza, N.; Priller, Josef; Ecker, Daniel

doi:10.1016/j.nurt.2007.10.053

Cited by 2 publications

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“…Likewise, a phase I study examining the safety and tolerability of phenylbutyrate in HD (PHEND-HD) has recently been completed (Clinical Trials identifier—NCT00212316). In this study, phenylbutyrate was found to be both safe and well tolerated in early symptomatic HD subjects taking 15 g daily, and levels leukocyte histone acetylation were measurable, indicating that HDAC inhibition was occurring in response to treatment (Moser et al 2008 ) A similar dose escalation/de-escalation study using sodium phenylbutyrate in HD patients agreed with the MTD of 15 g daily (Hogarth et al 2007 ), and at 12 g/daily was found to correct gene expression of a 12 gene biomarker set previously identified by this group (Borovecki et al 2005 ).…”

Section: Hdacs Er Stress and Pro-inflammatory Pathways In Hdmentioning

confidence: 78%

Targeting Huntington’s disease through histone deacetylases

Gray

2011

Clin Epigenet

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Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD.

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Section: Hdacs Er Stress and Pro-inflammatory Pathways In Hdmentioning

confidence: 78%

Targeting Huntington’s disease through histone deacetylases

Gray

2011

Clin Epigenet

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Epigenetic Treatment of Neurological Disease

Gray

2011

Epigenomics

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Neurological disease, and in particular neurodegenerative diseases, cause significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with these conditions remain limited, and generally, only provide modest symptomatic relief. Aberrant epigenetic post-translational modifications of proteins are emerging as important elements in the pathogenesis of neurological disease. Using Alzheimer's disease and Huntington's disease as examples in the following article, some of latest data linking both the histone code and the various proteins that regulate this code to the pathogenesis of neurological disease are discussed. The current evidence suggesting that pharmacologically targeting one such family, the histone deacetylases, may be of potential benefit in the treatment of such diseases is also discussed. Finally, some of the potential mechanisms to specifically target these proteins within the neurological setting are discussed.

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HD Unmet Clinical Research Needs: Perspective From the Pre-Manifest HD Population

Cited by 2 publications

References 1 publication

Targeting Huntington’s disease through histone deacetylases

Targeting Huntington’s disease through histone deacetylases

Epigenetic Treatment of Neurological Disease

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