Navigation Links
Feinstein scientists identify abnormal disease pathway in dystonia
Date:4/12/2011

MANHASSET, NY -- Scientists tried creating a laboratory model of idiopathic torsion dystonia, a neurological condition marked by uncontrolled movements, particularly twisting and abnormal postures. But the genetic defect that causes dystonia in humans didn't seem to work in the laboratory models that showed no symptoms whatsoever.

Now, a team of scientists at The Feinstein Institute for Medical Research have figured out why and the finding could lead to ways to test novel treatments. Aziz M. Ulug, PhD, and his colleagues at the Feinstein's Center for Neurosciences wanted to understand why some people with a gene that causes dystonia never get symptoms and others with the same mutation are disabled by the abnormal movements. Since the first dystonia gene was identified in the 1990s, scientists have observed that most people who carry this mutation never develop symptoms.

Last year, a team led by David Eidelberg, MD, head of the Feinstein Institute's Center for Neuroscience, figured out why the majority of these mutation carriers are protected from symptoms they have an additional lesion that evens the score. In an article published in the Journal of Neuroscience, the team described two separate areas along the brain pathway that links the cerebellum to the motor cortex. The integrity of the pathway in these two regions together determines whether a mutation carrier will display clinical manifestations of the disease.

New advances in diffusion imaging in humans led to the discovery that there were two places along the motor pathway that seemed to stop the flow of neural signals from one part of the circuit to the other. Those with only one lesion in the circuit developed the debilitating movements and those with two lesions did not. "We found a consistent cerebellar pathway problem in all DYT1 carriers. When we went back and looked at those without symptoms, we saw that they had an additional lesion downstream in the portion of the pathway connecting directly to the motor cortex," said Dr. Eidelberg. "This second area of pathway disruption abrogated the effects of the first lesion."

Normally, the cerebellum (a region that controls movement) puts the breaks on the motor cortex by potentiating inhibition at the cortical level. It is likely that mutation carriers have a developmental problem in the flow of neural signals along this circuit such that the brain cannot inhibit an unwanted movement. With the second pathway lesion, Dr. Eidelberg explained, "the flow is shut off and the abnormal activity stops."

The Feinstein team has since looked at laboratory models to try to figure out why this second lesion is protective. Since the identification of the DYT1 gene, scientists have been trying to create a genetic model of the movement disorder. But when they placed the same mutation in an experimental mouse model, there was a major problem: no symptoms. Dr. Ulug's team used a novel magnetic resonance approach to understand why the mutant animals were clinically normal. They found that the mutant mice displayed the same two pathway abnormalities that were found in the human gene carriers. However, the animals had dual lesions across the board, resembling the 70 percent of carriers who fail to display clinical manifestations of the disease. The study was published in the Proceedings of the National Academy of Sciences.

Knowing this critical piece of the puzzle may enable scientists to create true laboratory models of the disease with symptoms that mimic what is seen in patients. These findings may help to design treatments to make the symptomatic carriers of dystonia genes more like their unaffected counterparts with the same genetic mutation.


'/>"/>

Contact: Jamie Talan
jtalan@nshs.edu
516-562-1232
North Shore-Long Island Jewish (LIJ) Health System
Source:Eurekalert

Related medicine news :

1. Feinstein Institute to share $5M US Department of Defense grant
2. Scientists find potential benefit of hypericin for recurrent brain tumors
3. Scientists Use Computer to Read Human Thoughts
4. UCSD scientists receive prestigious Hartwell Biomedical Research Awards
5. Fox Chase scientists report interplay between cancer and aging in mice
6. U-M scientists find potential driver of some aggressive prostate cancers
7. Scientists Spot 4 New Alzheimers Genes
8. Scientists identify KRAS rearrangements in metastatic prostate cancer
9. Smithsonian scientists find declining rainfall is a major influence for migrating birds
10. Scientists devise targeted therapy strategy for rare form of childhood cancer
11. Scientists Create Autism-Like Traits in Mice
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/9/2016)... ... December 09, 2016 , ... Cellairis is a worldwide ... repairs on iPhone , iPad and Samsung Galaxy devices with premium ... Walmart in order to maximize convenience and accessibility for customers. While customers do their ...
(Date:12/9/2016)... ... December 09, 2016 , ... An inventor from Cana, Va., wanted ... all types of amusement park rides. , The patent-pending SAFETY STRAP FOR AMPUTEES improves ... use and could be set up in a matter of minutes, or even seconds. ...
(Date:12/9/2016)... Harrisburg, PA (PRWEB) , ... December 09, 2016 ... ... concussion education program through the Pennsylvania Cable Network (PCN) during the summer of ... Brain Injury Implementation Grant provided by the United States Department of Health and ...
(Date:12/8/2016)... NY (PRWEB) , ... December 08, 2016 , ... ... is pleased to announce that “Natural Language Processing–Enabled and Conventional Data Capture Methods ... in JMIR Medical Informatics . , Results of the comparative usability study ...
(Date:12/8/2016)... ... 2016 , ... David J. Dykeman , Ginger Pigott , and ... speak at DeviceTalks West, Dec. 12, 2016, at the Fairmont Newport Beach in California. ... firm’s global Life Sciences & Medical Technology Group have been featured speakers at every ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... , 8 de dezembro de 2016  A Mederi Therapeutics Inc ... Stretta, um tratamento não cirúrgico para a doença do refluxo gastroesofágico (DRGE). ... ... Live Stretta procedure performed and broadcast ... Endoscopy at Wuhan Union Hospital ...
(Date:12/8/2016)... , Dec. 8, 2016  Pennsylvania Physician ... of Drug and Alcohol Programs Gary Tennis ... insomnia medications, known as benzodiazepines, developed with the ... "Benzodiazepines are medications that are frequently prescribed for ... they are used with opioid pain medications, benzodiazepines ...
(Date:12/8/2016)... 2016 True Health Diagnostics today announced ... services and management expertise to hospital systems throughout ... more doctors and patients to benefit from state-of-the-art ... Logo - http://photos.prnewswire.com/prnh/20161208/447162LOGO ... pressure to contain costs, have struggled to keep ...
Breaking Medicine Technology: