Featured Research

from universities, journals, and other organizations

Fatal Brain Disease At Work Well Before Symptoms Appear

Date:
June 10, 2009
Source:
University of Florida
Summary:
Scientists have discovered why a paralyzing brain disorder speeds along more rapidly in some patients than others -- a finding that may finally give researchers an entry point toward an effective treatment for amyotrophic lateral sclerosis, often referred to as ALS or Lou Gehrig's disease.

University of Florida scientists have discovered why a paralyzing brain disorder speeds along more rapidly in some patients than others — a finding that may finally give researchers an entry point toward an effective treatment for amyotrophic lateral sclerosis, often referred to as ALS or Lou Gehrig's disease.

Of more than 100 possible mutations of a single gene inherited by people with familial ALS, the mutations most inclined to produce clumps of problematic cellular debris known as "protein aggregates" appear to be associated with quicker progress of the disease, according to researchers with the University of Florida's McKnight Brain Institute writing online this week in Human Molecular Genetics.

Meanwhile, in a separate study recently online in the Proceedings of the National Academy of Sciences, scientists describe how these protein clumps — long considered a defining characteristic of ALS — do not cause the disease, but appear later on, increasing in number between onset of weakness and paralysis in patients.

Together, these findings suggest that the deadly course of the disease is linked to the formation of these protein clumps, even though the sickness may have been well under way.

"Blocking aggregation of these proteins could be a therapeutic target for individuals with this genetic mutation," said David Borchelt, Ph.D., a professor of neuroscience and director of the SantaFe HealthCare Alzheimer's Disease Research Center at UF's McKnight Brain Institute. "Right now, there is little that can be done to help these patients."

ALS involves the death of nerve cells that stretch from the brain to the spinal cord, and from the spinal cord to muscles. It strikes people between the ages of 40 and 70, according to the ALS Association. An estimated 30,000 Americans have the disease at any given time.

Patients usually have a life expectancy of two to five years, with some notable exceptions, such as Cambridge University scientist and author Stephen Hawking, who has survived for more than 40 years since his diagnosis.

The cause of ALS is unknown in about 80 percent of cases, but 10 percent to 20 percent of ALS cases can be traced to an inherited genetic defect. No matter the cause, scientists believe that a basic cellular process in which amino acids are folded into proteins goes wrong in ALS. The misfolded proteins cannot perform their intended function. Instead, they form the troublesome protein aggregates.

UF's research centered around one gene that produces an enzyme called superoxide dismutase 1, or SOD1. Although SOD1 performs an important role in cell maintenance by warding off dangerous molecules known as free radicals, 146 different mutations in the SOD1 gene have been identified in patients with inherited ALS.

UF scientists, including doctoral student Mercedes Prudencio with Dr. Peter Andersen of Umea University in Sweden, analyzed data from ALS patients to correlate the disease features with more than 30 different variants of SOD1. They found that the mutations most associated with protein aggregation are generally predictive of a more rapid disease progression.

In the PNAS study, UF researchers with investigators from the University of Texas Health Science Center in San Antonio pinpointed when the protein clumping begins and how long the disease has been at work before symptoms actually appear.

By studying SOD1 in mice genetically engineered with a form of ALS, UF doctoral student Celeste Karch demonstrated that the protein clumps appear in spinal cord tissues later in the disease, about the same time that symptoms appear, but well after cell damage occurs from nerve loss and the formation of fluid-filled pockets called vacuoles.

The finding suggests the aggregated proteins may elude normal cellular "housecleaning" methods, or their formation is heightened by stress conditions in the cell.

"As the disease enters the symptomatic stage in mice, the buildup of protein is rapid and dramatic," Borchelt said. "However, the formation of these aggregates is not the whole story. It is well established that significant damage to the nervous system occurs well before the symptoms appear. The uncontrolled misfolding of SOD1 seems to be confined to the late stage of disease, which is when symptoms first appear, giving hope that treatments targeting this process could be beneficial."

Furthermore, the findings suggest that there is a larger therapeutic window to treat ALS, if scientists can find a way to diagnose the disease before the hallmark protein clumping begins.

"Many scientists had accepted that protein aggregation was tied to the causation of ALS," said Joan Selverstone Valentine, Ph.D., a UCLA professor of chemistry and biochemistry who did not participate in the study. "But this research shows these aggregates form during disease progression, not initiation. It is important to know what to look for as an early cause of the disease and what causes it to get more severe. That means we have to look for something upstream of aggregation as a cause, as well as understand the steps in the progress. If you can prevent or halt the aggregation, you can stop the disease in its tracks. That's as good as a cure if it can be done early enough."


Story Source:

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


Cite This Page:

University of Florida. "Fatal Brain Disease At Work Well Before Symptoms Appear." ScienceDaily. ScienceDaily, 10 June 2009. <www.sciencedaily.com/releases/2009/06/090608182545.htm>.
University of Florida. (2009, June 10). Fatal Brain Disease At Work Well Before Symptoms Appear. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2009/06/090608182545.htm
University of Florida. "Fatal Brain Disease At Work Well Before Symptoms Appear." ScienceDaily. www.sciencedaily.com/releases/2009/06/090608182545.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Cases Keep Coming for Monrovia's Island Hospital

Ebola Cases Keep Coming for Monrovia's Island Hospital

AFP (Oct. 1, 2014) A look inside Monrovia's Island Hospital, a key treatment centre in the fight against Ebola in Liberia's capital city. Duration: 00:34 Video provided by AFP
Powered by NewsLook.com
Ebola Puts Stress on Liberian Health Workers

Ebola Puts Stress on Liberian Health Workers

AP (Oct. 1, 2014) The Ebola outbreak is putting stress on first responders in Liberia. Ambulance drivers say they are struggling with chronic shortages of safety equipment and patients who don't want to go to the hospital. (Oct. 1) Video provided by AP
Powered by NewsLook.com
Doctors Reassure Public Ebola Patient Won't Cause Outbreak

Doctors Reassure Public Ebola Patient Won't Cause Outbreak

Newsy (Sep. 30, 2014) After the announcement that the first U.S. patient had been diagnosed with Ebola, doctors were quick to say a U.S. outbreak is highly unlikely. Video provided by Newsy
Powered by NewsLook.com
TX Hospital Confirms Patient Admitted With Ebola

TX Hospital Confirms Patient Admitted With Ebola

AP (Sep. 30, 2014) Medical officials from Texas Health Presbyterian Hospital confirm they are treating a patient with the Ebola virus, the first case found in the US. (Sept. 30 Video provided by AP
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