Huntington’s disease Clinical Trials Corner: February 2018

© 2018 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0)In the second edition of the Huntington’s Disease Clinical Trials Corner we list all currently registered and ongoing clinical trials, summarise the top-line results of the recently-announced IONIS-HTTRX trial (NCT02519036), expand on Wave Life Sciences’ PRECISION-HD1 (NCT03225833) and PRECISION-HD2 (NCT03225846), and cover one recently finished trial: the FIRST-HD deutetrabenazine trial (NCT01795859).info:eu-repo/semantics/publishedVersio

Clinical trials corner: September 2017

© 2017 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0).Clinical Trials Corner of Journal of Huntington’s Disease will regularly review ongoing and recently completed clinical trials in Huntington’s disease. In this inaugural issue, we list all currently registered and ongoing clinical trials, expand on LEGATO-HD and IONIS-HTTRx, and cover two recently finished trials: Amaryllis and Pride-HD.info:eu-repo/semantics/publishedVersio

Modeling and visualizing uncertainty in gene expression clusters using Dirichlet process mixtures

Although the use of clustering methods has rapidly become one of the standard computational approaches in the literature of microarray gene expression data, little attention has been paid to uncertainty in the results obtained. Dirichlet process mixture (DPM) models provide a nonparametric Bayesian alternative to the bootstrap approach to modeling uncertainty in gene expression clustering. Most previously published applications of Bayesian model-based clustering methods have been to short time series data. In this paper, we present a case study of the application of nonparametric Bayesian clustering methods to the clustering of high-dimensional nontime series gene expression data using full Gaussian covariances. We use the probability that two genes belong to the same cluster in a DPM model as a measure of the similarity of these gene expression profiles. Conversely, this probability can be used to define a dissimilarity measure, which, for the purposes of visualization, can be input to one of the standard linkage algorithms used for hierarchical clustering. Biologically plausible results are obtained from the Rosetta compendium of expression profiles which extend previously published cluster analyses of this data

Huntington's Disease Clinical Trials Corner: November 2022

In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the PIVOT HD (PTC518), and SIGNAL (pepinemab) trials, and list all currently registered and ongoing clinical trials in Huntington's disease.We also introduce a 'breaking news' section highlighting recent updates about the SELECT HD, uniQure AMT-130, and VIBRANT HD clinical trials

Huntington's Disease Clinical Trials Corner: July 2023

In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the GENERATION HD2 (tominersen) and on the Asklepios Biopharmaceutical/BrainVectis trial with AB-1001. We also comment on the recent findings from the PROOF-HD trial, and list all currently registered and ongoing clinical trials in Huntington's disease

Huntington's disease clinical trials corner: April 2022

In this edition of the Huntington's Disease Clinical Trials Corner we expand on GENERATION HD1, PRECISION-HD1 and PRECISION-HD2, SELECT-HD, and VIBRANT-HD trials, and list all currently registered and ongoing clinical trials in Huntington's disease

Tetrabenazine versus deutetrabenazine for Huntington's disease : twins or distant cousins?

© 2017 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: Tetrabenazine is the only US Food and Drug Administration‐approved drug for Huntington's disease, and deutetrabenazine was recently tested against placebo. A switching‐trial from tetrabenazine to deutetrabenazine is underway, but no head‐to‐head, blinded, randomized controlled trial is planned. Using meta‐analytical methodology, the authors compared these molecules. Methods: RCTs comparing tetrabenazine or deutetrabenazine with placebo in Huntington's disease were searched. The authors assessed the Cochrane risk‐of‐bias tool, calculated indirect treatment comparisons, and applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: The evidence network for this report comprised 1 tetrabenazine trial and 1 deutetrabenazine trial, both against placebo. Risk of bias was moderate in both. Participants in the tetrabenazine and deutetrabenazine trials did not differ significantly on motor scores or adverse events. Depression and somnolence scales significantly favored deutetrabenazine. Conclusion: There is low‐quality evidence that tetrabenazine and deutetrabenazine do not differ in efficacy or safety. It is important to note that these results are likely to remain the only head‐to‐head comparison between these 2 compounds in Huntington's disease.info:eu-repo/semantics/publishedVersio

Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients.

Quantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously

Neurofilament Light Protein as a Potential Blood Biomarker for Huntington's Disease in Children

BACKGROUND: Juvenile-onset Huntington's disease (JOHD) is a rare and particularly devastating form of Huntington's disease (HD) for which clinical diagnosis is challenging and robust outcome measures are lacking. Neurofilament light protein (NfL) in plasma has emerged as a prognostic biomarker for adult-onset HD. METHODS: We performed a retrospective analysis of samples and data collected between 2009 and 2020 from the Kids-HD and Kids-JHD studies. Plasma samples from children and young adults with JOHD, premanifest HD (preHD) mutation carriers, and age-matched controls were used to quantify plasma NfL concentrations using ultrasensitive immunoassay. RESULTS: We report elevated plasma NfL concentrations in JOHD and premanifest HD mutation-carrying children. In pediatric HD mutation carriers who were within 20 years of their predicted onset and patients with JOHD, plasma NfL level was associated with caudate and putamen volumes. CONCLUSIONS: Quantifying plasma NfL concentration may assist clinical diagnosis and therapeutic trial design in the pediatric population. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society