Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Discover Genetic Link Between Both Types of ALS

06.05.2010
Finding could ultimately lead to therapy for ALS

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.

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.

Marla Paul is the health sciences editor.
Contact her at marla-paul@northwestern.edu

Marla Paul | EurekAlert!
Further information:
http://www.northwestern.edu

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Gold shines through properties of nano biosensors

17.08.2017 | Physics and Astronomy

Greenland ice flow likely to speed up: New data assert glaciers move over sediment, which gets more slippery as it gets wetter

17.08.2017 | Earth Sciences

Mars 2020 mission to use smart methods to seek signs of past life

17.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>