Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Feinstein scientists identify abnormal disease pathway in dystonia

13.04.2011
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.

There are half a million people in the United States with dystonia. The brains of people with inherited dystonia are normal at autopsy and the exact cause of their movement abnormality is unknown.

About The Feinstein Institute for Medical Research

Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in cancer, leukemia, lymphoma, Parkinson's disease, Alzheimer's disease, psychiatric disorders, substance abuse, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, neuroimmunology and medicinal chemistry. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient, annually enrolling some 10,000 subjects into clinical research programs.

Jamie Talan | EurekAlert!
Further information:
http://www.nshs.edu

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>