Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Share

April 08, 2014; 82 (10 Supplement) May 01, 2014

Safety and Tolerability of Selisistat for the Treatment of Huntington’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (S47.004)

Ralf Reilmann, Ferdinando Squitieri, Josef Priller, Carsten Saft, Caterina Mariotti, Sigurd Suessmuth, Andrea Nemeth, Sarah Tabrizi, Oliver Quarrell, David Craufurd, Hugh Rickards, Anne Rosser, Darpo Borje, Tessari Michaela, Szynol Angieszka, David Fischer, Douglas Macdonald, Ignacio Munoz-Sanjuan, Robert Pacifici, Chris Frost, Ruth Farmer, Bernhard Landwehrmeyer, Goran Westerberg
First published April 9, 2014,
Ralf Reilmann
20Neurology University of Muenster - UKM Muenster Germany
10Neurology George-Huntington-Institute Muenster Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ferdinando Squitieri
11IRCC Neuromed Pozzilli Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Josef Priller
7Psychiatry Charité University Berlin Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carsten Saft
2Bochum Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Caterina Mariotti
5Milan Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sigurd Suessmuth
6Ulm Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrea Nemeth
15Neurology Oxford University Oxford United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarah Tabrizi
3London United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Oliver Quarrell
21University of Sheffield Sheffield United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Craufurd
19University of Manchester Manchester United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hugh Rickards
17University of Birmingham Birmingham United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne Rosser
18University of Cardiff Cardiff United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Darpo Borje
22University of Stockolm Stockholm Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tessari Michaela
13Leiden Unniversity Leiden Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Szynol Angieszka
13Leiden Unniversity Leiden Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Fischer
12Leiden University Leiden Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas Macdonald
8CHDI-Foundation Los Angeles CA United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ignacio Munoz-Sanjuan
9CHDI-Foundation Princeton NJ United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Pacifici
4Los Angeles CA United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chris Frost
1
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruth Farmer
14London School of Hygiene and Tropical Medicine London United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernhard Landwehrmeyer
23University of Ulm Ulm Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Goran Westerberg
16Siena Biotech Siena Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Citation
Safety and Tolerability of Selisistat for the Treatment of Huntington’s Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (S47.004)
Ralf Reilmann, Ferdinando Squitieri, Josef Priller, Carsten Saft, Caterina Mariotti, Sigurd Suessmuth, Andrea Nemeth, Sarah Tabrizi, Oliver Quarrell, David Craufurd, Hugh Rickards, Anne Rosser, Darpo Borje, Tessari Michaela, Szynol Angieszka, David Fischer, Douglas Macdonald, Ignacio Munoz-Sanjuan, Robert Pacifici, Chris Frost, Ruth Farmer, Bernhard Landwehrmeyer, Goran Westerberg
Neurology Apr 2014, 82 (10 Supplement) S47.004;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
0

Share

  • Article
  • Info & Disclosures
Loading

Abstract

OBJECTIVE: To evaluate safety and tolerability of selisistat over 12 weeks in patients with Huntington’s Disease (HD). BACKGROUND: Selisistat is a first-in-class SirT1 inhibitor shown to be safe and well tolerated in healthy volunteers and HD patients in short-term studies. DESIGN/METHODS: This was a double-blind, placebo-controlled, international multi-centre study of selisistat in individuals with Stage I-III HD. Participants (30-70 yrs) with genetically confirmed HD, a Unified Huntington Disease Rating Scale (UHDRS) Total Motor Score of >=5 and a Total Functional Capacity >=5 were randomized (1:1:1) to selisistat 50 or 200 mg or placebo once daily for 12 weeks. Safety and tolerability were evaluated by monitoring adverse events, vital signs, ECG and laboratory safety data throughout the study. Blood sampling for pharmacokinetics and soluble mutant huntingtin levels were collected throughout. RESULTS: A total of 144 patients were randomized and 125 patients (87%) completed the study. There were 9 serious adverse events, three in each treatment group, including one death in the placebo group. The most common adverse events were reversible increases in liver function tests without accompanying increases in bilirubin. All of these occurred in the selisistat groups; while most of these increases were <3×ULN, three events were classified as serious. No clinically relevant changes in the UHDRS readouts were observed during the relatively short treatment period. Levels of soluble mutant huntingtin in peripheral blood mononuclear cells showed borderline statistically significant (p=0.058 , p=0.075) increases of similar magnitude at 12 weeks compared to placebo in the 50mg and 200mg groups respectively, that reverted to levels consistent with the placebo group at follow-up. CONCLUSIONS: Apart from increases in liver function tests in a subset of patients, selisistat was safe and well tolerated, and a trend for modulation of the levels of soluble mutant huntingtin was observed. Study supported by: Siena Biotech SpA.

Disclosure: Dr. Reilmann has received personal compensation for activities with Novartis, Siena Biotech, Neursearch Inc., Ipsen, Teva Neuroscience, Lundbeck, and Medivation. Dr. Reilmann has received personal compensation for activities with the Journal of Huntington's Disease. Dr. Reilmann has received research support from the High-Q-Foundation, the Cure Huntington's Disease Initiative Foundation, the Deutsche Forschungsgemeinschaft, and the European Huntington's Disease Network. Dr. Squitieri has nothing to disclose. Dr. Priller has nothing to disclose. Dr. Saft has received personal compensation for activities with Temmler Pharma as a speaker. Dr. Saft has received research support from Neurosearch, Novartis and Siena Biotech. Dr. Mariotti has nothing to disclose. Dr. Suessmuth has nothing to disclose. Dr. Nemeth has nothing to disclose. Dr. Tabrizi has nothing to disclose. Dr. Quarrell has nothing to disclose. Dr. Craufurd has nothing to disclose. Dr. Rickards has nothing to disclose. Dr. Rosser has nothing to disclose. Dr. Borje has nothing to disclose. Dr. Michaela has nothing to disclose. Dr. Angieszka has nothing to disclose. Dr. Fischer has nothing to disclose. Dr. Macdonald has nothing to disclose. Dr. Munoz-Sanjuan has nothing to disclose. Dr. Pacifici has received personal compensation for activities with Science Applications International Corp. as a consultant. Dr. Frost has nothing to disclose. Dr. Farmer has nothing to disclose. Dr. Landwehrmeyer has received personal compensation for activities with Siena Biotech SPA and AOP Orphan. Dr. Landwehrmeyer has received research support from the European Commission, CHDI Foundation, Medivation, NeuroSearch, Novartis, Medesis, and Amarin. Dr. Westerberg has nothing to disclose.

Thursday, May 1 2014, 1:00 pm-2:45 pm

  • Copyright © 2014 by AAN Enterprises, Inc.

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
  • Info & Disclosures
Advertisement

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials

Dr. Nicole Sur and Dr. Mausaminben Hathidara

► Watch

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published
Neurology: 100 (22)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise