Featured Research

from universities, journals, and other organizations

Proposed drug may reverse Huntington's disease symptoms: Single treatment gives long-term improvement in animals

Date:
June 20, 2012
Source:
University of California, San Diego Health Sciences
Summary:
With a single drug treatment, researchers can silence the mutated gene responsible for Huntington’s disease, slowing and partially reversing progression of the fatal neurodegenerative disorder in animal models.

Stained mouse neurons.
Credit: Image courtesy of Taylor Bayouth.

With a single drug treatment, researchers at the Ludwig Institute for Cancer Research at the University of California, San Diego School of Medicine can silence the mutated gene responsible for Huntington's disease, slowing and partially reversing progression of the fatal neurodegenerative disorder in animal models.

The findings are published in the June 21, 2012 print issue of the journal Neuron.

Researchers suggest the drug therapy, tested in mouse and non-human primate models, could produce sustained motor and neurological benefits in human adults with moderate and severe forms of the disorder. Currently, there is no effective treatment.

Huntington's disease afflicts approximately 30,000 Americans, whose symptoms include uncontrolled movements and progressive cognitive and psychiatric problems. The disease is caused by the mutation of a single gene, which results in the production and accumulation of toxic proteins throughout the brain.

Don W. Cleveland, PhD, professor and chair of the UC San Diego Department of Cellular and Molecular Medicine and head of the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research, and colleagues infused mouse and primate models of Huntington's disease with one-time injections of an identified DNA drug based on antisense oligonucleotides (ASOs). These ASOs selectively bind to and destroy the mutant gene's molecular instructions for making the toxic huntingtin protein.

The singular treatment produced rapid results. Treated animals began moving better within one month and achieved normal motor function within two. More remarkably, the benefits persisted, lasting nine months, well after the drug had disappeared and production of the toxic proteins had resumed.

"For diseases like Huntington's, where a mutant protein product is tolerated for decades prior to disease onset, these findings open up the provocative possibility that transient treatment can lead to a prolonged benefit to patients," said Cleveland. "This finding raises the prospect of a 'huntingtin holiday,' which may allow for clearance of disease-causing species that might take weeks or months to re-form. If so, then a single application of a drug to reduce expression of a target gene could 'reset the disease clock,' providing a benefit long after huntingtin suppression has ended."

Beyond improving motor and cognitive function, researchers said the ASO treatment also blocked brain atrophy and increased lifespan in mouse models with a severe form of the disease. The therapy was equally effective whether one or both huntingtin genes were mutated, a positive indicator for human therapy.

Cleveland noted that the approach was particularly promising because antisense therapies have already been proven safe in clinical trials and are the focus of much drug development. Moreover, the findings may have broader implications, he said, for other "age-dependent neurodegenerative diseases that develop from exposure to a mutant protein product" and perhaps for nervous system cancers, such as glioblastomas.

Co-authors are first author Holly B. Kordasiewicz, Melissa M. McAlonis, Kimberly A. Pytel and Jonathan W. Artates, Ludwig Institute for Cancer Research and UC San Diego Department of Cellular and Molecular Medicine; Lisa M. Stanek, Seng H. Cheng and Lamya S. Shihabuddin, Genzyme Corporation; Edward V. Wancewicz, Curt Mazur, Gene Hung and C. Frank Bennett, Isis Pharmaceuticals; and Andreas Weiss, Novartis Institutes for BioMedical Research.

Funding for this research came, in part, from the CHDI Foundation.


Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kordasiewicz et al. Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis. Neuron, June 21, 2012

Cite This Page:

University of California, San Diego Health Sciences. "Proposed drug may reverse Huntington's disease symptoms: Single treatment gives long-term improvement in animals." ScienceDaily. ScienceDaily, 20 June 2012. <www.sciencedaily.com/releases/2012/06/120620132924.htm>.
University of California, San Diego Health Sciences. (2012, June 20). Proposed drug may reverse Huntington's disease symptoms: Single treatment gives long-term improvement in animals. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2012/06/120620132924.htm
University of California, San Diego Health Sciences. "Proposed drug may reverse Huntington's disease symptoms: Single treatment gives long-term improvement in animals." ScienceDaily. www.sciencedaily.com/releases/2012/06/120620132924.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins