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:6/24/2016)... ... June 24, 2016 , ... The Haute Beauty ... Barry M. Weintraub as a prominent plastic surgeon and the network’s newest partner. ... and the most handsome men, look naturally attractive. Plastic surgery should be invisible.” ...
(Date:6/24/2016)... Frederick, Maryland (PRWEB) , ... June 24, 2016 ... ... Mid-Atlantic Angels is actively feeding the Frederick area economy by obtaining investment capital ... support over the past 2½ years that have already resulted in more than ...
(Date:6/24/2016)... ... 2016 , ... Venture Construction Group (VCG) sponsors Luke’s Wings ... at the Woodmont Country Club at 1201 Rockville Pike, Rockville, Maryland, 20852. The ... members that have been wounded in battle and their families. Venture Construction Group is ...
(Date:6/24/2016)... ... June 24, 2016 , ... Advanced Plastic Surgery ... Arizona pageant as its official Medspa Sponsor. Dr. Josh Olson, a board-certified plastic ... , Dr. Olson says the decision to support the pageant in an ...
(Date:6/24/2016)... ... June 24, 2016 , ... To succeed under value-based ... however, are unsure how to move forward, given the need to sustain current ... forward tailored to an organization’s specific needs. , PYA Principal Martie Ross states, ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016 Research and ... Excipients Market by Type (Organic Chemical (Sugar, Petrochemical, Glycerin), ... Topical, Coating, Parenteral) - Global Forecast to 2021" ... The global pharmaceutical excipients market is projected ... CAGR of 6.1% in the forecast period 2016 to ...
(Date:6/23/2016)... 23, 2016 Roche (SIX: RO, ROG; OTCQX: ... its Elecsys BRAHMS PCT (procalcitonin) assay as a dedicated ... shock. With this clearance, Roche is the first IVD ... solution for sepsis risk assessment and management. ... and PCT levels in blood can aid clinicians in ...
(Date:6/23/2016)... June 23, 2016 Capricor ... ), a biotechnology company focused on the discovery, ... that patient enrollment in its ongoing randomized HOPE-Duchenne ... exceeded 50% of its 24-patient target. Capricor expects ... third quarter of 2016, and to report top ...
Breaking Medicine Technology: