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Author: Elise Kayson (11)


Tetrabenazine is efficacious for chorea control; however, tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a double-blind, placebo-controlled study.
To evaluate the safety and explore the efficacy of conversion from tetrabenazine to deutetrabenazine in patients with chorea associated with Huntington disease (HD).

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Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial.

JAMA 2016 Jul;316(1):40-50
, Samuel Frank, Claudia M Testa, David Stamler, Elise Kayson, Charles Davis, Mary C Edmondson, Shari Kinel, Blair Leavitt, David Oakes, Christine O'Neill, Christina Vaughan, Jody Goldstein, Margaret Herzog, Victoria Snively, Jacquelyn Whaley, Cynthia Wong, Greg Suter, Joseph Jankovic, Joohi Jimenez-Shahed, Christine Hunter, Daniel O Claassen, Olivia C Roman, Victor Sung, Jenna Smith, Sarah Janicki, Ronda Clouse, Marie Saint-Hilaire, Anna Hohler, Denyse Turpin, Raymond C James, Ramon Rodriguez, Kyle Rizer, Karen E Anderson, Hope Heller, Alexis Carlson, Susan Criswell, Brad A Racette, Fredy J Revilla, Frederick Nucifora, Russell L Margolis, MaryJane Ong, Tilak Mendis, Neila Mendis, Carlos Singer, Monica Quesada, Jane S Paulsen, Thomas Brashers-Krug, Amanda Miller, Jane Kerr, Richard M Dubinsky, Carolyn Gray, Stewart A Factor, Elaine Sperin, Eric Molho, Mary Eglow, Sharon Evans, Rajeev Kumar, Christina Reeves, Ali Samii, Sylvain Chouinard, Monica Beland, Burton L Scott, Patrick T Hickey, Sherali Esmail, Wai Lun Alan Fung, Clare Gibbons, Lina Qi, Amy Colcher, Cory Hackmyer, Andrew McGarry, Kevin Klos, Mark Gudesblatt, Lori Fafard, Laura Graffitti, Daniel P Schneider, Rohit Dhall, Joanne M Wojcieszek, Kathrin LaFaver, Andrew Duker, Erin Neefus, Hilary Wilson-Perez, David Shprecher, Paola Wall, Karen A Blindauer, Lynn Wheeler, James T Boyd, Emily Houston, Eric S Farbman, Pinky Agarwal, Shirley W Eberly, Arthur Watts, Pierre N Tariot, Andrew Feigin, Scott Evans, Chris Beck, Constance Orme, Jon Edicola, Emily Christopher
Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity.
To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease.
Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (nā€‰=ā€‰45) or placebo (nā€‰=ā€‰45) in a double-blind fashion at 34 Huntington Study Group sites.

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Clinical-Genetic Associations in the Prospective Huntington at Risk Observational Study (PHAROS): Implications for Clinical Trials.

JAMA Neurol 2016 Jan;73(1):102-10
, Kevin Michael Biglan, Ira Shoulson, Karl Kieburtz, David Oakes, Elise Kayson, M Aileen Shinaman, Hongwei Zhao, Megan Romer, Anne Young, Steven Hersch, Jack Penney, Karen Marder, Jane Paulsen, Kimberly Quaid, Eric Siemers, Caroline Tanner, William Mallonee, Greg Suter, Richard Dubinsky, Carolyn Gray, Martha Nance, Scott Bundlie, Dawn Radtke, Sandra Kostyk, Corrine Baic, James Caress, Francis Walker, Victoria Hunt, Christine O'Neill, Sylvain Chouinard, Stewart Factor, Timothy Greenamyre, Cathy Wood-Siverio, Jody Corey-Bloom, David Song, Guerry Peavy, Carol Moskowitz, Melissa Wesson, Ali Samii, Thomas Bird, Hillary Lipe, Karen Blindauer, Frederick Marshall, Carol Zimmerman, Jody Goldstein, Diana Rosas, Peter Novak, John Caviness, Charles Adler, Amy Duffy, Vicki Wheelock, Teresa Tempkin, David Richman, Lauren Seeberger, Roger Albin, Kelvin L Chou, Brad Racette, Joel S Perlmutter, Susan Perlman, Yvette Bordelon, Wayne Martin, Marguerite Wieler, Blair Leavitt, Lynn Raymond, Joji Decolongon, Lorne Clarke, Joseph Jankovic, Christine Hunter, Robert A Hauser, Juan Sanchez-Ramos, Sarah Furtado, Oksana Suchowersky, Mary Lou Klimek, Mark Guttman, Rustom Sethna, Andrew Feigin, Marie Cox, Barbara Shannon, Alan Percy, Leon Dure, Madaline Harrison, William Johnson, Donald Higgins, Eric Molho, Constance Nickerson, Sharon Evans, Douglas Hobson, Carlos Singer, Nestor Galvez-Jimenez, Kathleen Shannon, Cynthia Comella, Christopher Ross, Marie H Saint-Hilaire, Claudia Testa, Adam Rosenblatt, Penelope Hogarth, William Weiner, Peter Como, Rajeev Kumar, Candace Cotto, Julie Stout, Alicia Brocht, Arthur Watts, Shirley Eberly, Christine Weaver, Tatiana Foroud, James Gusella, Marcy MacDonald, Richard Myers, Stanley Fahn, Clifford Shults
Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials.
To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational Study (PHAROS).
A prospective, multicenter, longitudinal cohort study was conducted at 43 US and Canadian Huntington Study Group research sites from July 9, 1999, through December 17, 2009.

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We aimed to describe the clinical phenotype conferred by the intermediate-length huntingtin allele CAG repeat expansion in a population-based study.
The Prospective Huntington At Risk Observational Study (PHAROS) enrolled adults at risk for Huntington disease (HD). They were assessed approximately every 9 months with the Unified Huntington's Disease Rating Scale (UHDRS) by investigators unaware of participants' gene status.

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To evaluate the safety and tolerability of latrepirdine in Huntington disease (HD) and explore its effects on cognition, behavior, and motor symptoms.
Double-blind, randomized, placebo-controlled trial.
Multicenter outpatient trial.

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Genetic testing in Huntington disease, an inherited ultimately fatal neurodegenerative disorder, is infrequent despite wide availability. Factors influencing the decision to pursue testing are largely unknown. We conducted a prospective longitudinal observational study of 1,001 individuals in North America who were at risk for Huntington disease who had not pursued genetic testing prior to enrollment.

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Previous studies of emotion recognition suggest that detection of disgust relies on processing within the basal ganglia and insula. Research involving individuals with symptomatic and pre-diagnostic Huntington's disease (HD), a disease with known basal ganglia atrophy, has generally indicated a relative impairment in recognizing disgust. However, some data have suggested that recognition of other emotions (particularly fear and anger) may also be affected in HD, and a recent study found fear recognition deficits in the absence of other emotion-recognition impairments, including disgust.

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Previous studies of verbal episodic memory in pre-diagnostic Huntington's disease (HD) have yielded mixed results; some evidence suggests that memory decline is evident prior to the onset of pronounced neurological signs of HD, whereas other data indicate that memory function remains normal throughout the pre-diagnostic period. This study examines verbal episodic memory in a sample of CAG expanded individuals who have not yet been clinically diagnosed, and who represent a wide range of points along the continuum from health to disease. The Hopkins Verbal Learning Test-Revised (HVLT-R) was administered to 479 participants (428 with the HD CAG expansion and 51 without), and performance was compared to neurobiological indices of disease progression, including a DNA-based estimate of proximity to clinical diagnosis, magnetic resonance imaging (MRI) measures of striatal volume, and neurologist ratings of motor signs.

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The optimal design and outcome measures for preventive clinical trials in neurodegenerative diseases are unknown.
To examine measures that may be associated with disease in the largest cohort ever recruited of prediagnosed individuals carrying the gene expansion for Huntington disease (HD).
The Predict-HD study is a multicenter observational research study in progress at 17 sites in the United States, 4 in Canada, and 3 in Australia.

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With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntington's disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy-five clinicians experienced in the evaluation of patients with early HD and six non-clinicians were shown a videotape compiled from the film archives of the United States-Venezuela Collaborative HD Research Project. Observers were asked to rate a 2-3-minute segment of the motor examination for each of 17 at-risk subjects.

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