Navigation Links
Toxin from brain cells triggers neuron loss in human ALS model
Date:2/6/2014

NEW YORK, NY (February 6, 2014) In most cases of amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, a toxin released by cells that normally nurture neurons in the brain and spinal cord can trigger loss of the nerve cells affected in the disease, Columbia researchers reported today in the online edition of the journal Neuron.

The toxin is produced by star-shaped cells called astrocytes and kills nearby motor neurons. In ALS, the death of motor neurons causes a loss of control over muscles required for movement, breathing, and swallowing. Paralysis and death usually occur within 3 years of the appearance of first symptoms.

The report follows the researchers' previous study, which found similar results in mice with a rare, genetic form of the disease, as well as in a separate study from another group that used astrocytes derived from patient neural progenitor cells. The current study shows that the toxins are also present in astrocytes taken directly from ALS patients.

"I think this is probably the best evidence we can get that what we see in mouse models of the disease is also happening in human patients," said the study's senior author, Serge Przedborski, MD, PhD, the Page and William Black Professor of Neurology (in Pathology and Cell Biology), Vice Chair for Research in the Department of Neurology, and co-director of Columbia's Motor Neuron Center.

The findings also are significant because they apply to the most common form of ALS, which affects about 90 percent of patients. Scientists do not know why ALS develops in these patients; the other 10 percent of patients carry one of 27 genes known to cause the disease.

"Now that we know that the toxin is common to most patients, it gives us an impetus to track down this factor and learn how it kills the motor neurons," Dr. Przedborski said. "Its identification has the potential to reveal new ways to slow down or stop the destruction of the motor neurons."

In the study, Dr. Przedborski and study co-authors Diane Re, PhD, and Virginia Le Verche, PhD, associate research scientists, removed astrocytes from the brain and spinal cords of six ALS patients shortly after death and placed the cells in petri dishes next to healthy motor neurons. Because motor neurons cannot be removed from human subjects, they had been generated from human embryonic stem cells in the Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, also at CUMC.

Within two weeks, many of the motor neurons had shrunk and their cell membranes had disintegrated; about half of the motor neurons in the dish had died. Astrocytes removed from people who died from causes other than ALS had no effect on the motor neurons. Nor did other types of cells taken from ALS patients.

The researchers confirmed that the cause of the motor neurons' death was a toxin released into the environment by immersing healthy motor neurons in the astrocytes' culture media. The presence of the media, even without astrocytes, killed the motor neurons.

How the Toxin Triggers Motor Neuron Death

The researchers have not yet identified the toxin released by the astrocytes. But they did discover the nature of the neuronal death process triggered by the toxin.The toxin triggers a biochemical cascade in the motor neurons that essentially causes them to undergo a controlled cellular explosion.

Drs. Przedborski, Re, and Le Verche found that they could prevent astrocyte-triggeredmotor neuron death by inhibiting one of the key components of this molecular cascade.

These findings may lead to a way to prevent motor neuron death in patients and potentially prolong life. But the therapeutic potential of such inhibition is far from clear. "For example, we don't know if this would leave patients with living but dysfunctional neurons," Dr. Przedborski said. The researchers are now testing the idea of inhibition in animal models of ALS.

New Human Cell Model of ALS Will Speed Identification of Potential Therapies

The development of new therapies for ALS has been disappointing, with more than 30 clinical trials ending with no new treatments since the 1995 FDA approval of riluzole.

The lack of progress may be partly because animal models used to study ALS do not completely recreate the human disease. The new all-human cell model of ALS created for the current study may improve scientists' ability to identify useful drug targets, particularly for the most common form of the disease.

"Although there are many neurodegenerative disorders, only for a handful do we have access to a simplified model that is relevant to the disease and can therefore potentially be used for high-throughput drug screening. So this model is quite special," Dr. Przedborski said. "Here we have a spontaneous disease phenotype triggered by the relevant tissue that causes human illness. That's one important thing. The other important thing is that this model is derived entirely from human elements. This is probably the closest, most natural model of human ALS that we can get in a dish."


'/>"/>

Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert  

Related medicine news :

1. NIH-created toxin can kill HIV-infected cells that persist despite treatment
2. How to Sleep Away Harmful Brain Toxins Discussed in Health Nutrition News Video
3. Bel Marra Health Reports on Recent Research Revealing a Dangerous Toxin Linked to Increased Risk of Stroke
4. Research Report on Feed Mycotoxin Absorbent Market in China
5. Environmental toxins linked to heart defects
6. Diet Doc Hormone Diets & Weight Loss Plans Announces Detox Formula, Designed to Cleanse the Liver of Dangerous Toxins & Avoid Weight Loss Plateaus
7. Quality Treatment for Biotoxin Related Illness is Getting Easier to Find
8. Neurotoxin effectively relieves bone cancer pain in dogs, Penn researchers find
9. New Studies Linking Environmental Toxins to Infertility Validate Benefits of Fairhaven Health's FertileDetox
10. European Food Safety Testing Market (Pathogen, GMO, Toxin, Pesticide) Worth $4,068.8 Million by 2018 - New Report by MarketsandMarkets
11. Diet Doc Weight Loss Plans Announces New Detox Formula, Designed to Promote Safe and Rapid Weight Loss By Cleansing the Body of Harmful Toxins
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Toxin from brain cells triggers neuron loss in human ALS model
(Date:12/4/2016)... ... December 03, 2016 , ... ... to funding innovative lymphoma research and serving the lymphoma community through a comprehensive ... Swirl: A Wine Tasting Event in New York City, with long-time partners The ...
(Date:12/4/2016)... ... ... While James Earl Jones is known for myriad roles on stage and ... Page". One of the forthcoming episodes examines mammogram techniques; a very important part of ... due to early detection. Like any other disease, treatments have a much higher chance ...
(Date:12/4/2016)... , ... December 03, 2016 , ... ... growing Entrepreneurial Company in the Dallas area” Tuesday evening at the 26th Annual ... Hotel, presented by SMU's Cox School’s Caruth Institute for Entrepreneurship. Dallas 100™, co-founded ...
(Date:12/4/2016)... Newport Beach, CA (PRWEB) , ... December 04, ... ... youthful appearance without undergoing major cosmetic surgery can now take advantage of a ... is an advanced skin rejuvenation treatment that reduces the appearance of age spots, ...
(Date:12/4/2016)... ... December 04, 2016 , ... Responsible dental care hinges ... brush properly to achieve optimal results. This important necessity inspired an inventor from Las ... a way to ensure that people break or avoid bad techniques of brushing the ...
Breaking Medicine News(10 mins):
(Date:12/4/2016)... Blueprint Medicines Corporation (NASDAQ: BPMC ... kinase medicines for patients with genomically defined diseases, ... trial evaluating BLU-285, an investigational medicine for the ... Blueprint Medicines is developing BLU-285 as a potent, ... 90 to 95 percent of patients with SM ...
(Date:12/4/2016)... HANOVER, N.J. , Dec. 3, 2016  Results ... (crizanlizumab, formerly SelG1), an anti-P-selectin antibody, reduced the median ... 45.3% compared to placebo (1.63 vs 2.98, p=0.010) in ... today announced that the data are being featured in ... American Society of Hematology (ASH) Annual Meeting and presented ...
(Date:12/2/2016)... - bioLytical lanza el INSTI HIV Self Test para el mercado africano ... Continue Reading ... New: INSTI Self Test! (PRNewsFoto/bioLytical ... bioLytical Laboratories (la "Compañía"), un líder mundial en ... de su INSTI HIV Self Test  a África con una versión de menor ...
Breaking Medicine Technology: