Tolerability and efficacy of the monoaminergic stabilizer (−)-OSU6162 (PNU-96391A) in Huntington’s disease: a double-blind cross-over study

2014 ◽  
Vol 26 (5) ◽  
pp. 298-306 ◽  
Author(s):  
Angelica Kloberg ◽  
Radu Constantinescu ◽  
Marie Karin Lena Nilsson ◽  
Maria Lizzie Carlsson ◽  
Arvid Carlsson ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scales ◽  
Short Form ◽  
Primary Objective ◽  
Double Blind ◽  
Good Tolerability ◽  
Motor Functions ◽  
Clinical Investigator ◽  
The Individual

ObjectiveTo evaluate the safety (primary objective) and efficacy (secondary objective) of (−)-OSU6162 in Huntington’s disease (HD).MethodsIn a double-blind, cross-over trial, patients with HD were randomly assigned to start treatment on either (−)-OSU6162 or placebo. After 4 weeks, those patients who initially received active drug were switched to placebo for another 4 weeks, and vice versa. During the first week the (−)-OSU6162 dose was 15 mg twice daily, during the second week 30 mg twice daily, and during the last 2 weeks 45 mg twice daily. Motor, cognitive, mental and social functions were rated by the clinical investigator or by self-assessment, using established rating scales.ResultsFifteen patients fulfilling inclusion and exclusion criteria completed the study. (−)-OSU6162 was well tolerated by all patients and no adverse effects were observed. (−)-OSU6162 treatment significantly improved the Short Form 36 Vitality score, mainly due to an improvement of the individual item ‘worn-out’ (VT3). In addition, an improvement of depressive symptoms was found using Beck Depression Inventory. In contrast to a general trend of improvement in several non-motor variables only small and non-significant differences between (−)-OSU6162 and placebo were found regarding motor functions.Conclusions(−)-OSU6162 offers promise for the treatment of HD, as a drug with good tolerability, capable of improving the patients’ experienced non-motor functions such as energy and mood and thus alleviating symptoms of great importance for their quality of life.

Pridopidine for the treatment of motor function in patients with Huntington's disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial

2011 ◽  
Vol 10 (12) ◽  
pp. 1049-1057 ◽  
Author(s):  
Justo Garcia de Yebenes ◽  
Bernhard Landwehrmeyer ◽  
Ferdinando Squitieri ◽  
Ralf Reilmann ◽  
Anne Rosser ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Motor Function ◽  
Controlled Trial ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals Antidopaminergic treatment is associated with reduced chorea and irritability but impaired cognition in Huntington’s disease (Enroll-HD)

2020 ◽  
Vol 91 (6) ◽  
pp. 622-630
Author(s):  
Kate L Harris ◽  
Wei-Li Kuan ◽  
Sarah L Mason ◽  
Roger A Barker
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Case Reports ◽  
Controlled Trial ◽  
Rate Of Change ◽  
Control Group ◽  
Open Label ◽  
Double Blind ◽  
Before And After ◽  
Rate Of Decline

ObjectivesAlterations in dopamine neurotransmission underlie some of the clinical features of Huntington’s disease (HD) and as such are a target for therapeutic intervention, especially for the treatment of chorea and some behavioural problems. However, justification for such an intervention is mainly based on case reports and small open label studies and the effects these drugs have on cognition in HD remain unclear.MethodsIn this study, we used the Enroll-HD observational database to assess the effects of antidopaminergic medication on motor, psychiatric and cognitive decline, over a 3-year period. We first looked at the annual rate of decline of a group of HD patients taking antidopaminergic medication (n=466) compared with an untreated matched group (n=466). The groups were matched on specified clinical variables using propensity score matching. Next, we studied a separate group of HD patients who were prescribed such medications part way through the study (n=90) and compared their rate of change before and after the drugs were introduced and compared this to a matched control group.ResultsWe found that HD patients taking antidopaminergic medication had a slower progression in chorea and irritability compared with those not taking such medications. However, this same group of patients also displayed significantly greater rate of decline in a range of cognitive tasks.ConclusionIn conclusion we found that antidopaminergic treatment is associated with improvements in the choreic movements and irritability of HD but worsens cognition. However, further research is required to prospectively investigate this and whether these are causally linked, ideally in a double-blind placebo-controlled trial.

Huntington's disease: prediction and prevention

1988 ◽  
Vol 319 (1194) ◽  
pp. 285-298 ◽  
Keyword(s):  
At Risk ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Late Onset ◽  
Predictive Test ◽  
Prediction And Prevention ◽  
Feasible Alternative ◽  
Dna Restriction ◽  
The Individual ◽  
First Time

The identification of a DNA restriction fragment length polymorphism closely linked to Huntington’s disease on the short arm of chromosome 4 has for the first time allowed presymptomatic prediction to be undertaken in first-degree relatives at risk. The late and variable onset of this dominantly inherited disorder makes such prediction a powerful and potentially valuable aid in genetic counselling, but in the absence of effective therapy there are serious ethical reservations concerning such a predictive test. The new developments have stimulated an active and informative debate among professionals and family members on whether and how predictive tests should be used. Guidelines have emerged which should be useful not only for Huntington’s disease, but for other serious late-onset neurogenetic disorders. Meanwhile, studies in Wales and elsewhere have not only confirmed the original linkage but have excluded multi-locus heterogeneity as a significant problem. Genetic prediction for the individual at risk remains critically dependent on a suitable family structure, present in only a minority of families in Wales. A more feasible alternative for most families is prenatal exclusion, which can allow risk prediction for a pregnancy without altering the situation for the person at risk. This approach has already been applied in Wales; the experience gained will be useful in full prediction, which is currently being introduced.

Rating scales for cognition in Huntington's disease: Critique and recommendations

2017 ◽  
Vol 33 (2) ◽  
pp. 187-195 ◽  
Author(s):  
Tiago A. Mestre ◽  
Anne-Catherine Bachoud-Lévi ◽  
Johan Marinus ◽  
Julie C. Stout ◽  
Jane S. Paulsen ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scales

A randomized, double-blind, placebo-controlled phase Ib study with selisistat (SEN0014196) in patients with Huntington's disease

Basal Ganglia ◽  
2013 ◽  
Vol 3 (1) ◽  
pp. 47
Author(s):  
S.D. Süssmuth ◽  
G.B. Landwehrmeyer ◽  
S.J. Tabrizi ◽  
C. Andersen ◽  
M. DiBacco ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Phase Ib

Q23 A double blind, cross over, placebo-controlled, phase II trial of Sativex in Huntington's Disease

2012 ◽  
Vol 83 (Suppl 1) ◽  
pp. A62.2-A62 ◽  
Author(s):  
JG Caldentey ◽  
JL Lopéz-Sendón ◽  
P Trigo ◽  
C Ruiz ◽  
GG Ribas ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Double Blind

scholarly journals Analysis of the impact of Tominersen (IONIS-HTTRX/RG6042) in the treatment of Huntington’s disease: A systematic review

2021 ◽  
Author(s):  
Gustavo Soares Gomes Barros Fonseca ◽  
Maria Luiza Mendes Machado ◽  
Paulo Victor Protásio Bezerra
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Messenger Rna ◽  
Randomized Clinical Trials ◽  
Therapeutic Response ◽  
Gene Encoding ◽  
Double Blind ◽  
Electronic Search ◽  
The Impact ◽  
To Receive

Introduction: Huntington’s disease (HD) is a congenital pathology of a hereditary, neurodegenerative and progressive character, with a high mortality rate. This pathology is caused by repeated expansions of a single CAG codon in the gene encoding huntingtin. To date, several attempts to prevent and delay such a mutation have been carried out in patients. However, a promising drug, Tominersen, formerly called IONIS HTTRx/ RG6042, is in the testing phase and has shown a favorable therapeutic response, which acts directly on the messenger RNA of the gene encoding huntingtin (HTT). The drug, whose route of administration is intrathecal in bolus, intercepts and destroys the messenger before the corrupted protein can work. The present study aims to analyze the impact of Tominersen in the treatment of patients with HD and to evaluate its prognosis. Methods: The present study is a systematic literature review, in which an electronic search was performed in the PubMed, SciELO, Web of Science and Google Scholar databases. Results: In one of the double-blind randomized clinical trials (n = 46), 34 were assigned to receive the drug. The group that received Tominersen showed a decrease in the concentration of mutant HTT in cerebrospinal fluid after 28 days. In another study (n = 791), the GENERATION HD1 clinical trial is currently taking place and will last for 25 months. Conclusion: Tominersen decreases the concentration of HTT, that is, it suppressed the protein responsible for HD. Studies related to the drug are still very recent and require extra attention.

Huntington’s Disease Quality of Life Battery for Carers--Short Form

2019 ◽  
Author(s):  
Aimee Aubeeluck ◽  
Edward J. N. Stupple ◽  
Malcolm B. Schofield ◽  
Alis C. Hughes ◽  
Lucienne van der Meer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Short Form
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