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 Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

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: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>