Featured Research

from universities, journals, and other organizations

Genetic link between both types of ALS discovered

Date:
May 6, 2010
Source:
Northwestern University
Summary:
Researchers have discovered a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease also known as Lou Gehrig's disease. Researchers linked a rare genetic cause to most cases of ALS, clearing the way for therapy based on a known molecular target.

Researchers from Northwestern University Feinberg School of Medicine have discovered a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease also known as Lou Gehrig's disease.

Related Articles


Researchers found that a protein called FUS forms characteristic skein-like cytoplasmic inclusions in spinal motor neurons in most cases of ALS. Mutations in this gene have been previously linked to a small subset of familial ALS cases. Researchers thus linked a rare genetic cause to most cases of ALS, clearing the way for rational therapy based on a known molecular target.

The study was recently published online in the Annals of Neurology.

ALS is a disease in which muscle-controlling nerve cells in the brain and spinal cord (motor neurons) die, resulting in rapidly progressive paralysis and death usually within three to five years of the onset of symptoms. Most cases of ALS are of unknown etiology and appear as sporadic ALS. About 5 to 10 percent of ALS cases are familial. Some forms of familial ALS are caused by genetic mutations in specific genes. Mutations in the Cu/Zn superoxide dismutase gene (SOD1) account for approximately 20 percent of familial ALS cases. Mutations in the TAR DNA-binding protein gene (TDP43) and FUS gene occur in about 4 to 5 percent of the familial ALS cases. Altogether, mutations in specific genes have been identified in about 30 percent of familial ALS cases. In contrast to familial ALS, the etiology and the pathogenic mechanisms underlying sporadic ALS -- 90 percent of all ALS -- has remained largely unknown. Understanding the causes and pathogenic mechanisms of sporadic ALS is the major challenge in this disease.

For this study, researchers examined the post-mortem spinal cords and brains of 100 cases, 78 with ALS and 22 in a control group. They found FUS pathology in the spinal cords of all the ALS cases, except for a few cases with SOD1 mutations. But FUS pathology was not present in control cases without ALS.

"This is a game changer because it establishes a connection in the development of sporadic ALS with a known cause of familial ALS," said senior author Teepu Siddique, M.D., the Les Turner ALS Foundation/Herbert C. Wenske Professor of the Davee Department of Neurology and Clinical Neurosciences at Feinberg and a neurologist at Northwestern Memorial Hospital.

"Our finding opens up a new field of investigation for rational therapy for all of ALS," Siddique added. "This is the holy grail of researchers in this field."

"There hasn't been a therapy for most of ALS, because the cause was unknown," Siddique said. "Three genes have been identified in ALS, but the problem has been connecting inherited ALS to sporadic ALS." "We identified the FUS pathology in sporadic ALS and most familial ALS cases," said Han-Xiang Deng, M.D., associate professor of neurology at Feinberg and lead author of the paper. "The patients with the FUS pathology may account for about 90 percent of all ALS cases. Our findings suggest that pathological interaction of FUS with other proteins is a common theme in motor neuron degeneration in the vast majority of the ALS cases. We believe that this is a major step forward in formulating a common pathogenic pathway for motor neuron degeneration. Importantly, it may offer a novel avenue for developing therapies through targeting these FUS-containing inclusions." The one exception to the new finding is when familial ALS is associated with a mutation on the SOD1 gene. In those patients and in the mutant SOD1 transgenic mouse models, researchers did not find evidence of FUS pathology.

"This tells us that it follows a different pathway of pathogenesis, so treatment for this form of the disease would have to be different," Deng said.

The study is supported by the National Institutes of Health, the Les Turner ALS Foundation, the Vena E. Schaff ALS Research Fund, the Harold Post Research Professorship, the Herbert and Florence C. Wenske Foundation, the David C. Asselin MD Memorial Fund and the Les Turner ALS Foundation/Herbert and Florence C. Wenske Professorship.


Story Source:

The above story is based on materials provided by Northwestern University. The original article was written by Marla Paul. Note: Materials may be edited for content and length.


Journal Reference:

  1. Han-Xiang Deng, Hong Zhai, Eileen H. Bigio, Jianhua Yan, Faisal Fecto, Kaouther Ajroud, Manjari Mishra, Senda Ajroud-Driss, Scott Heller, Robert Sufit, Nailah Siddique, Enrico Mugnaini, Teepu Siddique. FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Annals of Neurology, 2010; DOI: 10.1002/ana.22051

Cite This Page:

Northwestern University. "Genetic link between both types of ALS discovered." ScienceDaily. ScienceDaily, 6 May 2010. <www.sciencedaily.com/releases/2010/05/100505173014.htm>.
Northwestern University. (2010, May 6). Genetic link between both types of ALS discovered. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2010/05/100505173014.htm
Northwestern University. "Genetic link between both types of ALS discovered." ScienceDaily. www.sciencedaily.com/releases/2010/05/100505173014.htm (accessed November 23, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, November 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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