Featured Research

from universities, journals, and other organizations

Essential clue to Huntington's disease solution found

Date:
July 29, 2013
Source:
McMaster University
Summary:
Researchers have discovered a solution to a long-standing medical mystery in Huntington's disease (HD).

Researchers at McMaster University have discovered a solution to a long-standing medical mystery in Huntington's disease (HD).

HD is a brain disease that can affect 1 in about 7,000 people in mid-life, causing an increasing loss of brain cells at the centre of the brain. HD researchers have known what the exact DNA change is that causes Huntington's disease since 1993, but what is typically seen in patients does not lead to disease in animal models. This has made drug discovery difficult.

In this week's issue of the science journal, the Proceedings of the National Academy of Sciences, professor Ray Truant's laboratory at McMaster University's Department of Biochemistry and Biomedical Sciences of the Michael G. DeGroote School of Medicine reveal how they developed a way to measure the shape of the huntingtin protein, inside of cell, while still alive. They then discovered was that the mutant huntingtin protein that causes disease was changing shape. This is the first time anyone has been able to see differences in normal and disease huntingtin with DNA defects that are typical in HD patients.

They went on to show that they can measure this shape change in cells derived from the skin cells of living Huntington's disease patients.

"With mouse models, we know that some drugs can stop, and even reverse Huntington's disease, but now we know exactly why," said Truant. "The huntingtin protein has to take on a precise shape, in order to do its job in the cell. In Huntington's disease, the right parts of the protein can't line up to work properly. It's like trying to use a paperclip after someone has bent it out of shape."

The research also shows that the shape of disease huntingtin protein can be changed back to normal with chemicals that are in development as drugs for HD. "We can refold the paper clip," said Truant.

The methods they developed have been scaled up and used for large scale robotic drug screening, which is now ongoing with a pharmaceutical company. They are looking for drugs that can enter the brain more easily. Furthermore, they can tell if the shape of huntingtin has been corrected in patients undergoing drug trials, without relying on years to know if the HD is affected yet.

This research was a concerted effort from many sources: funding from the Canadian Foundation Institute and the Ontario Innovation Trust for an $11M microscopy centre at McMaster in 2006, ongoing support from the Canadian Institutes of Health Research, and important funding from the Toronto-based Krembil Foundation. The project was initiated with charity grant support from the Huntington Society of Canada, which allowed them to show this method was promising for further support.

The last piece of the puzzle was from the Huntington's disease patient community, with skin cell donations from living patients and unaffected spouses that allowed the team to look at real human disease.

There are eight other diseases that have a similar DNA defects as Huntington's disease, Truant's group is now using similar tools to develop assays to measure shape changes in those diseases, to see if this shapeshifting is common in other diseases.


Story Source:

The above story is based on materials provided by McMaster University. Note: Materials may be edited for content and length.


Journal Reference:

  1. N. S. Caron, C. R. Desmond, J. Xia, R. Truant. Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1301342110

Cite This Page:

McMaster University. "Essential clue to Huntington's disease solution found." ScienceDaily. ScienceDaily, 29 July 2013. <www.sciencedaily.com/releases/2013/07/130729161517.htm>.
McMaster University. (2013, July 29). Essential clue to Huntington's disease solution found. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2013/07/130729161517.htm
McMaster University. "Essential clue to Huntington's disease solution found." ScienceDaily. www.sciencedaily.com/releases/2013/07/130729161517.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Idaho Boy Helps Brother With Disabilities Complete Triathlon

Newsy (July 23, 2014) An 8-year-old boy helped his younger brother, who has a rare genetic condition that's confined him to a wheelchair, finish a triathlon. Video provided by Newsy
Powered by NewsLook.com
Thousands Who Can't Afford Medical Care Flock to Free US Clinic

Thousands Who Can't Afford Medical Care Flock to Free US Clinic

AFP (July 23, 2014) America may be the world’s richest country, but in terms of healthcare, the World Health Organisation ranks it 37th. Thousands turned out for a free clinic run by "Remote Area Medical" with a visit from the Governor of Virginia. Duration: 2:40 Video provided by AFP
Powered by NewsLook.com
Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. 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