Featured Research

from universities, journals, and other organizations

Human-cell-derived model of amyotrophic lateral sclerosis provides a new way to study the majority of cases

Date:
August 12, 2011
Source:
Nationwide Children's Hospital
Summary:
For decades, scientists have studied a laboratory mouse model that develops signs of the paralyzing disease amyotrophic lateral sclerosis (ALS) as they age. Researchers have now developed a new model of ALS, one that mimics sporadic ALS, which represents about 90 percent of all cases.

For decades, scientists have studied a laboratory mouse model that develops signs of the paralyzing disease amyotrophic lateral sclerosis (ALS) as they age. In a new study appearing in Nature Biotechnology, investigators at Nationwide Children's Hospital have developed a new model of ALS, one that mimics sporadic ALS, which represents about 90 percent of all cases.

ALS, commonly known as Lou Gehrig's disease, is characterized by the death of motor neurons, which are muscle-controlling nerve cells in the spinal cord. As these neurons die, the body's voluntary muscles weaken and waste away; death within five years of diagnosis is common. Only about 10 percent of ALS cases are familial meaning the disease runs in the family. The majority of ALS cases are sporadic, with no family history.

Mutations in the SOD1 gene are found in about one-fifth of people with familial ALS, and for decades, experts have theorized that the gene holds clues to sporadic ALS. Laboratory mice carrying human SOD1 mutations develop signs of ALS as they age, and have been widely used to investigate the causes and potential treatments for the disease. At the same time, however, researchers have questioned whether SOD1 mice are useful and whether SOD1 itself is relevant for understanding sporadic ALS. While dozens of potential therapies have shown promise in the mice, most have failed in patients.

"The mouse models capture a type of familial ALS that accounts for only two percent of all cases. The field has begged for new disease models that can provide a clear window into sporadic ALS," said senior author Brian Kaspar, PhD, principal investigator in the Center for Gene Therapy of The Research Institute at Nationwide Children's Hospital.

Nationwide Children's researchers attempted to develop such a model by isolating cells from patients' spinal tissue within a few days after death.

First, the team isolated neural progenitor cells from post-mortem spinal tissue of patients with ALS. Neural progenitor cells are the "parent" cells of neurons and astrocytes, cells of the central nervous system. They then coaxed these progenitor cells to develop into astrocytes. Next, the team combined the patient-derived astrocytes with mouse motor neurons. At first, the motor neurons grew normally, but after four days, they began to degenerate. By five days, the number of motor neurons reduced by about half compared to motor neurons that had been grown with control astrocytes. Similar results were seen when the motor neurons were grown with astrocytes from a patient with familial ALS, or with a cell culture broth that had been conditioned by astrocytes from any of the ALS patients. This suggests the ALS-derived astrocytes are releasing one or more unknown toxins.

Further experiments revealed that inflammatory responses and SOD1 may play a critical role in this toxicity. These results suggest that replacing astrocytes may be just as important as replacing motor neuron lost to the disease and that astrocytes and SOD1 need further investigation as targets for therapy.

"It has been a long road, but the hard work starts now," said Dr. Kaspar. "We still need to confront fundamental questions about what is happening to astrocytes and how they are killing motor neurons. And the ultimate goal is to identify therapies that will translate into helping humans."

The research was funded in part by the National Institutes of Health's National Institute of Neurological Disorders and Stroke, including a $1.7 million stimulus grant made possible by the American Recovery and Reinvestment Act.


Story Source:

The above story is based on materials provided by Nationwide Children's Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Amanda M Haidet-Phillips, Mark E Hester, Carlos J Miranda, Kathrin Meyer, Lyndsey Braun, Ashley Frakes, SungWon Song, Shibi Likhite, Matthew J Murtha, Kevin D Foust, Meghan Rao, Amy Eagle, Anja Kammesheidt, Ashley Christensen, Jerry R Mendell, Arthur H M Burghes, Brian K Kaspar. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nature Biotechnology, 2011; DOI: 10.1038/nbt.1957

Cite This Page:

Nationwide Children's Hospital. "Human-cell-derived model of amyotrophic lateral sclerosis provides a new way to study the majority of cases." ScienceDaily. ScienceDaily, 12 August 2011. <www.sciencedaily.com/releases/2011/08/110811094841.htm>.
Nationwide Children's Hospital. (2011, August 12). Human-cell-derived model of amyotrophic lateral sclerosis provides a new way to study the majority of cases. ScienceDaily. Retrieved August 27, 2014 from www.sciencedaily.com/releases/2011/08/110811094841.htm
Nationwide Children's Hospital. "Human-cell-derived model of amyotrophic lateral sclerosis provides a new way to study the majority of cases." ScienceDaily. www.sciencedaily.com/releases/2011/08/110811094841.htm (accessed August 27, 2014).

Share This




More Health & Medicine News

Wednesday, August 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WHO Calls for Ban on E-Cigarette Sales to Minors

WHO Calls for Ban on E-Cigarette Sales to Minors

AFP (Aug. 26, 2014) — The World Health Organization called Tuesday on governments should ban the sale of e-cigarettes to minors, warning that they pose a "serious threat" to foetuses and young people. Duration: 01:44 Video provided by AFP
Powered by NewsLook.com
Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Have You Ever Been 'Sleep Drunk?' 1 in 7 Has

Newsy (Aug. 26, 2014) — A study published in the journal "Neurology" interviewed more than 19,000 people and found 15 percent suffer from being "sleep drunk." Video provided by Newsy
Powered by NewsLook.com
Does Medical Marijuana Reduce Painkiller Overdose Deaths?

Does Medical Marijuana Reduce Painkiller Overdose Deaths?

Newsy (Aug. 26, 2014) — A new study found fewer deaths from prescription drug overdoses in states that have legalized medical marijuana. But experts disagree on the results. Video provided by Newsy
Powered by NewsLook.com
Official: British Ebola Sufferer Receiving Experimental Drug

Official: British Ebola Sufferer Receiving Experimental Drug

AFP (Aug. 26, 2014) — A British nurse infected with Ebola while working in Sierra Leone is being given the same experimental drug used on two US missionaries who have recovered for the disease, doctors in London say. Duration: 00:44 Video provided by AFP
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