Navigation Links
Researchers discover new clues about how amyotrophic lateral sclerosis develops
Date:3/31/2013

Johns Hopkins scientists say they have evidence from animal studies that a type of central nervous system cell other than motor neurons plays a fundamental role in the development of amyotrophic lateral sclerosis (ALS), a fatal degenerative disease. The discovery holds promise, they say, for identifying new targets for interrupting the disease's progress.

In a study described online in Nature Neuroscience, the researchers found that, in mice bred with a gene mutation that causes human ALS, dramatic changes occurred in oligodendrocytes cells that create insulation for the nerves of the central nervous system long before the first physical symptoms of the disease appeared. Oligodendrocytes located near motor neurons cells that govern movement died off at very high rates, and new ones regenerated in their place were inferior and unhealthy.

The researchers also found, to their surprise, that suppressing an ALS-causing gene in oligodendrocytes of mice bred with the disease while still allowing the gene to remain in the motor neurons profoundly delayed the onset of ALS. It also prolonged survival of these mice by more than three months, a long time in the life span of a mouse. These observations suggest that oligodendrocytes play a very significant role in the early stage of the disease.

"The abnormalities in oligodendrocytes appear to be having a negative impact on the survival of motor neurons," says Dwight E. Bergles, Ph.D., a co-author and a professor of neuroscience at the Johns Hopkins University School of Medicine. "The motor neurons seem to be dependent on healthy oligodendrocytes for survival, something we didn't appreciate before."

"These findings teach us that cells we never thought had a role in ALS not only are involved but also clearly contribute to the onset of the disease," says co-author Jeffrey D. Rothstein, M.D., Ph.D., a professor of neurology at Johns Hopkins and director of the Johns Hopkins Medicine Brain Science Institute.

Scientists have long believed that oligodendrocytes functioned only as structural elements of the central nervous system. They wrap around nerves, making up the myelin sheath that provides the "insulation" that allows nerve signals to be transmitted rapidly and efficiently. However, Rothstein and others recently discovered that oligodendrocytes also deliver essential nutrients to neurons, and that most neurons need this support to survive.

The Johns Hopkins team of Bergles and Rothstein published a paper in 2010 that described in mice with ALS an unexpected massive proliferation of oligodendrocyte progenitor cells in the spinal cord's motor neurons, and that these progenitors were being mobilized to make new oligodendrocytes. The researchers believed that these cells were multiplying because of an injury to oligodendrocytes, but they weren't sure what was happening. Using a genetic method of tracking the fate of oligodendrocytes, in the new study, the researchers found that cells present in young mice with ALS were dying off at an increasing rate in concert with advancing disease. Moreover, the development of the newly formed oligodendrocytes was stalled and they were not able to provide motor neurons with a needed source of cell nutrients.

To determine whether the changes to the oligodendrocytes were just a side effect of the death of motor neurons, the scientists used a poison to kill motor neurons in the ALS mice and found no response from the progenitors, suggesting, says Rothstein, that it is the mutant ALS gene that is damaging oligodendrocytes directly.

Meanwhile, in separate experiments, the researchers found similar changes in samples of tissues from the brains of 35 people who died of ALS. Rothstein says it may be possible to see those changes early on in the disease and use MRI technology to follow progression.

"If our research is confirmed, perhaps we can start looking at ALS patients in a different way, looking for damage to oligodendrocytes as a marker for disease progression," Rothstein says. "This could not only lead to new treatment targets but also help us to monitor whether the treatments we offer are actually working."

ALS, also known as Lou Gehrig's disease, named for the Yankee baseball great who died from it, affects nerve cells in the brain and spinal cord that control voluntary muscle movement. The nerve cells waste away or die, and can no longer send messages to muscles, eventually leading to muscle weakening, twitching and an inability to move the arms, legs and body. Onset is typically around age 50 and death often occurs within three to five years of diagnosis. Some 10 percent of cases are hereditary.

There is no cure for ALS and there is only one FDA-approved drug treatment, which has just a small effect in slowing disease progression and increasing survival.

Even though myelin loss has not previously been thought to occur in the gray matter, a region in the brain where neurons process information, the researchers in the new study found in ALS patients a significant loss of myelin in one of every three samples of human tissue taken from the brain's gray matter, suggesting that the oligodendrocytes were abnormal. It isn't clear if the oligodendrocytes that form this myelin in the gray matter play a different role than in white matter the region in the brain where signals are relayed.

The findings further suggest that clues to the treatment of other diseases long believed to be focused in the brain's gray matter such as Alzheimer's disease, Huntington's disease and Parkinson's disease may be informed by studies of diseases of the white matter, such as multiple sclerosis (MS). Bergles says ALS and MS researchers never really thought their diseases had much in common before.

Oligodendrocytes have been under intense scrutiny in MS, Bergles says. In MS, the disease over time can transform from a remitting-relapsing form in which myelin is attacked but then is regenerated when existing progenitors create new oligodendrocytes to re-form myelin to a more chronic stage in which oligodendrocytes are no longer regenerated. MS researchers are working to identify new ways to induce the creation of new oligodendrocytes and improve their survival. "It's possible that we may be able to dovetail with some of the same therapeutics to slow the progression of ALS," Bergles says.


'/>"/>

Contact: Stephanie Desmon
sdesmon1@jhmi.edu
410-955-8665
Johns Hopkins Medicine
Source:Eurekalert

Related medicine news :

1. Researchers discover primary role of the olivocochlear efferent system
2. Researchers Test Implanted Brain Stimulator for Alzheimers
3. Moffitt Researchers help lead international efforts that find new genetic links to ovarian cancer
4. Researchers successfully map fountain of youth
5. Moffitt researchers analyze HPV vaccination disparities among girls from low-income families
6. Notre Dame researchers scoring a win-win with novel set of concussion diagnostic tools
7. Researchers form new nerve cells &#8211 directly in the brain
8. Moffitt Cancer Center researchers design small molecule to disrupt cancer-causing protein
9. UW researchers discover the brain origins of variation in pathological anxiety
10. Researchers decode biology of blood and iron disorders mapping out novel future therapies
11. Researchers developing antiviral drug to combat contagious norovirus
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... ... Ellevate Network, the leading network for professional women, brought together some of ... their inaugural Summit in New York City in June. The event was livestreamed with ... 3 million. To watch the Mobilize Women video, click here . , ...
(Date:10/13/2017)... ... October 13, 2017 , ... ... giving viewers the lowdown on sciatica in a new episode of "Success Files," ... on current events and innovation and investigates each subject in-depth with passion and ...
(Date:10/13/2017)... ... October 13, 2017 , ... “America On The Brink”: the Christian history of ... Brink” is the creation of published author, William Nowers. Captain Nowers and his ... veteran, he spent thirty years in the Navy. Following his career as a ...
(Date:10/12/2017)... ... 2017 , ... Planet Fitness, one of the largest and fastest growing franchisors ... a flagship location in Covington, LA at 401 N. U.S. Highway 190, in January ... Office Depot in the Holiday Square shopping center. Its location allows it to serve ...
(Date:10/12/2017)... , ... October 12, 2017 , ... The American College ... to Carol Friedman, PhD, FACMI, during the Opening Session of AMIA’s Annual Symposium in ... , In honor of Morris F. Collen, a pioneer in the field of medical ...
Breaking Medicine News(10 mins):
(Date:9/12/2017)... 12, 2017   EcoVadis , the leading platform for environmental, social ... annual edition of its Global CSR Risk and Performance Index. The report ... based on Scorecard Ratings that analyzed nearly 800,000 data points across the ... ... ...
(Date:9/12/2017)... 12, 2017  ValGenesis Inc., the global leader ... pleased to announce the appointment of Dr. ... Board of Directors and Chairman of Advisory Board ... science companies to manage their entire validation lifecycle ... in this process. Furthermore, ValGenesis VLMS enables rigorous ...
(Date:9/9/2017)... 8, 2017 Dealmed Medical Supplies, ... medical equipment, supplies, drugs, vaccines, and specialty medical products ... an agreement to acquire Vantage Medical Supplies, a major ... Holtsville, New York . ... and emerging medical practices, will operate under the Dealmed ...
Breaking Medicine Technology: